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These procedures were designed and tested for internal use by OSHA personnel. Mention of any company name or commercial product does not constitute endorsement by OSHA.

Related Information: Chemical Sampling - Enflurane, Halothane, Isoflurane

Method number: 103
 
Matrix: Air
 
Target concentration, TC:

enflurane halothane isoflurane
TC low high low high low high

ppm 1 75 1 50 1 75
mg/m3 7.5 566 8 403 7.5 566

 
OSHA PEL:
ACGIH TLV:
None
75 ppm (566 mg/m3) for enflurane
50 ppm (403 mg/m3) for halothane
 
Procedure: Samples are collected by drawing a known volume of air through standard size (6-mm o.d., 150/75 mg) Anasorb CMS or (6-mm o.d., 140/70 mg) Anasorb 747 tubes. Samples are desorbed with CS2 and analyzed by GC using a flame-ionization detector (FID).
 
Air volume
and sampling rate:
12 L at 0.05 L/min
 
Reliable quantitation limit:

enflurane halothane isoflurane
Anasorb CMS 747 CMS 747 CMS 747

ppb 25.0 40.7 24.4 21.3 23.0 23.5
µg/m3 189 307 197 172 174 177

 
Standard error of estimate
at the target concentration:

enflurane halothane isoflurane
Anasorb CMS 747 CMS 747 CMS 747

low TC 0.072 0.058 0.076 0.054 0.078 0.059
high TC 0.083 0.077 0.070 0.058 0.085 0.061

 
Special requirements: Samples collected on Anasorb CMS for halothane should be stored at reduced temperature following receipt at the laboratory until analysis.
 
Status of method: Evaluated method. This method has been subjected to the established evaluation procedures of the Organic Methods Evaluation Branch.
 
 
Date: May 1994 Chemist: Donald Burright

Organic Methods Evaluation Branch
OSHA Salt Lake Technical Center
Salt Lake City, UT 84165-0200

1. General Discussion

1.1 Background

1.1.1 History

The objective of this method is to eliminate the need to use two adsorbent tubes connected in series as specified for enflurane and halothane in OSHA Method 29 (Ref. 5.1), and to expand the methodology to include the newer anesthetic gases, isoflurane and desflurane. (Desflurane will appear as a separate method because it requires different analytical conditions.) Enflurane, halothane and isoflurane were each evaluated at two target concentrations because NIOSH recommended exposure limits (Refs. 5.2 and 5.3) are considerably lower than the current ACGIH TLVs (Ref. 5.4). For this reason, the method was evaluated at a lower target concentration of 1 ppm for all three analyses. Currently there are no OSHA PELs for these substances. Preliminary studies were performed with the following adsorbents: Anasorb CMS, Anasorb 747, Carbosieve S-III and activated coconut charcoal. Anasorb CMS and Anasorb 747 were both good candidates for an improved sampler as neither adsorbent required two tube in series. Evaluation tests were begun with both adsorbents in the anticipation that one would dearly surpass the other in performance. Since this did not occur, both were evaluated and are presented as sampling options.

ACGIH has recommended a TLV-TWA of 75 ppm for enflurane and 50 ppm for halothane (Ref. 5.4). The TLV for enflurane is based on the assumption enflurane is a safer anesthetic gas than halothane. The TLV for halothane is based on a comparison of toxicity and TLVs of trichloroethylene and chloroform. (Ref. 5.4) The ACGIH recommendations are the basis for setting the higher target concentrations of enflurane and halothane for the evaluation of this method. A higher target concentration of 75 ppm was set for isoflurane because it is a geometric isomer of enflurane. NIOSH has recommended that exposure to these halogenated anesthetic gases should be controlled with a 60-min ceiling value of 2 ppm (Ref. 5.2). The anesthetic gases are usually administered in conjunction with nitrous oxide.

1.1.2 Toxic effects (This section is for information only and should not be taken as the basis of OSHA policy.)

Current scientific evidence obtained from human and animal studies suggest that chronic exposure to anesthetic gases increase the risk of both spontaneous abortion and congenital abnormalities in offspring among female workers and wives of male workers. Risks of hepatic and renal diseases are also increased among exposed workers. (Ref 5.2) IARC states there is inadequate evidence for the carcinogenicity of enflurane, halothane and isoflurane in both animals and humans (Ref. 5.5).

Enflurane and isoflurane have similar health effects for acute exposure. An exposure may cause irritation and redness in eyes, dryness and irritation of skin, and irritation of the mouth and throat. If inhaled, headaches, dizziness, drowsiness, unconsciousness, and death can occur. (Refs. 5.6 and 5.7)

Acute exposures of halothane can cause severe irritation to the eyes, irritation of the skin, reduction of the blood pressure, dizziness, drowsiness, and unconsciousness. Chronic exposures can possibly cause cancer. (Ref. 5.8)

1.1.3 Workplace exposure

Enflurane, halothane and isoflurane are the most commonly used organic anesthetic gases. Occupational exposure may occur whenever anesthetics are used in operating rooms, dental offices and veterinary hospitals. The number of people potentially exposed was estimated to be 215,000 in 1977 (Ref. 5.2). This number is probably much higher today if the increase in the health care industry since 1977 is considered.

1.1.4 Physical properties and other descriptive information (Refs. 5.6 - 5.9)

enflurane halothane isoflurane
CAS number: 13838-16-9 151-67-7 26675-46-7
molecular weight: 184.49 197.39 184.49
boiling point, °:   56.5 50.2 48.5
color: colorless colorless colorless
specific gravity: 1.52 1.872 1.50
molecular formula: C3H2OClF5 C2HBrClF3 C3H2OClF5
vapor pressure,
kPa (mmHg):

25.1(188.6)
@22°C

32.4(243.3)
@20°C

34.9(261.8)
@22°C
odor: odorless mild ethereal
flash point, °: >200 none >200
solubility: miscible with
organic solvents
miscible with pet
ether and other fat solvents
miscible with
organic liquids
synonyms: Ethrane; 2-chloro-
1,1,2-trifluoroethyl
difluoromethyl
ether; methyl
flurether; Efrane;
Alyrane
Fluothrane;
2-bromo-2-chloro-
1,1,1-trifluoro-
ethane;
Rhodialothan
Forane; 1-chloro-
2,2,2-trigluoroethyl
difluoromethyl
ether; Aerrane;
Forene
structural formulas: structural formulas

The analyte air concentrations throughout this method are based on the recommended sampling and analytical parameters. Air concentrations listed in ppm are referenced to 25° and 101.3 kPa (760 mmHg).


1.2 Limit defining parameters

1.2.1 Detection limit of the analytical procedure

The detection limits of the analytical procedure are 92.8, 87.3 and 44.7 pg for enflurane, halothane and isoflurane respectively. These are the amounts of each analyte that will give a response that is significantly different from the background response of a reagent blank. (Sections 4.1 and 4.2)

1.2.2 Detection limit of the overall procedure

The detection limits of the overall procedure (mass per sample) are listed below. These are the amounts of each analyte spiked on the sampler that will give a response that is signfticantly different from the background response of a sampler blank. (Sections 4.1 and 4.3)

Table 1.2.2
Detection Limits of the Overall Procedure

adsorbent enflurane halothane isoflurane

Anasorb CMS 0.679 µg 0.709 µg 0.625 µg
7.50 ppb 7.32 ppb 6.91 ppb
56.6 µg/m3 59.1 µg/m3 52.1 µg/m3
Anasorb 747 1.105 µg 0.620 µg 0.639 µg
12.2 ppb 6.40 ppb 7.06 ppb
92.1 µg/m3 51.7 µg/m3 53.3 µg/m3

1.2.3 Reliable quantitation limit

The reliable quantitation limits (mass per sample) are listed below. These are the amounts of analyses spiked on a sampler that will give a signal that is considered the lower limit for precise quantitative measurements. (Section 4.4)

Table 1.2.3
Reliable Quantitation Limits

adsorbent enflurane halothane isonurane

Anasorb CMS 2.26 µg 2.36 µg 2.08 µg
25.0 ppb 24.4 ppb 23.0 ppb
188 µg/m3 197 µg/m3 173 µg/m3
Anasorb 747 3.68 µg 2.07 µg 2.13 µg
40.7 ppb 21.4 ppb 23.5 ppb
307 µg/m3 172 µg/m3 178 µg/m3

1.2.4 Precision (analytical Procedure)

The precisions of the analytical procedure are measured as the pooled relative standard deviation over a concentration range equivalent to the range of 0.5 to 2 times the target concentration. (Section 4.5)

Table 1.2.4
Precisions of the Analytical Procedure, %

target concn enflurane halothane isoflurane
1 ppm 2.77 1.39 3.50
50 ppm 1.37
75 ppm 2.27 2.83

1.2.5 Precision (overall procedure)

The precisions of the overall procedure at the 95% confidence level for the ambient temperature 15-18 day storage tests (at the target concentration) are listed below. This includes an additional 5% for sampling error. (Section 4.6)

Table 1.2.5.1
Precision of the Overall Procedure on Anasorb CMS, %

target concn enflurane halothane isoflurane

1 ppm 14.1 14.9‡ 15.3
50 ppm 13.7
75 ppm 16.3 16.6

‡ - refrigerated storage test at 4°


Table 1.2.5.2
Precision of the Overall Procedure on Anasorb 747, %

target concn enflurane halothane isoflurane

1 ppm 11.3 10.6 11.5
50 ppm 11.4
75 ppm 15.1 12.0

1.2.6 Recovery

The recoveries of enflurane, halothane and isoflurane from samples used in the 15-18 day storage tests remained above the values listed below when the samples were stored at 22°. (Section 4.7)

Table 1.2.6.1
Recovery from Anasorb CMS, %

target concn enflurane halothane isoflurane

1 ppm 94.6 97.1‡ 93.7
50 ppm 94.5
75 ppm 96.2   97.2

‡ - refrigerated storage test at 4°


Table 1.2.6.2
Recovery from Anasorb 747, %

target concn enflurane halothane isoflurane

1ppm 99.6 99.8 98.7
50 ppm 99.3
75 ppm 98.0 97.9

1.2.7 Reproducibility

Forty-eight samples collected from controlled test atmospheres, along with a draft copy of this procedure, were submitted for analysis by one of the OSHA Salt Lake Technical Center's service branch laboratories. The samples were analyzed after 17-23 days of storage at 4°. No indiividual sample result deviated from its theoretical value by more than the precision reported in Section 1.2.5. (Section 4.8)

2. Sampling Procedure

2.1 Apparatus

2.1.1 Samples are collected using a personal sampling pump calibrated, with the sampling device attached, within ±5% at the recommended flow rate.

2.1.2 Samples are collected with 7-cm × 4-mm i.d. × 6-mm o.d. glass sampling tubes packed with two sections of (150/75 mg) Anasorb CMS or (140/70 mg) Anasorb 747. The sections are held in place with a glass wool plug and two urethane foam plugs. For this evaluation, commercially prepared sampling tubes were purchased from SKC, Inc. (catalog nos. 226-121 and 226-81).

2.2 Reagents

None required.

2.3 Technique

2.3.1 Only properly trained personnel can sample in an operating room or dental office, this is necessary to be in compliance with OSHA's Exposure Control Plan for bloodborne pathogens. (Ref. 5.10)

2.3.2 Immediately before sampling, break off the ends of the sampling tube. All tubes should be from the same lot.

2.3.3 Attach the sampling tube to the sampling pump with flexible, non-crimping tubing. It is desirable to utilize sampling tube holders which have a protective cover to shield the employee from the sharp, jagged end of the sampling tube. Position the tube so that the sampled air first passes through the larger section.

2.3.4 Air being sampled should not pass through any hose or tubing before entering the sampling tube.

2.3.5 To avoid channeling, attach the sampler vertically with the larger section pointing downward, in the worker's breathing zone. Position the sampler so it does not impede work performance or safety.

2.3.6 After sampling for the appropriate time, immediately remove the sampling tube and seal it with plastic end caps.

2.3.7 In order to prevent occupational exposure to SLTC personnel, sampling tubes that may become contaminated with blood or other potentially infectious materials are to be examined prior to shipping and decontaminated (e.g., wiped off with bleach or other disinfectant) as necessary. Contaminated items are not to be placed or stored in areas where food is kept, and decontamination should be accomplished as soon as possible following the inspection where contamination occurred. Decontamination is not to take place in any area where food or drink is consumed. (Ref. 5.10)

2.3.8 Wrap each sample end-to-end with a Form OSHA-21 seal.

2.3.9 Submit at least one blank sample with each set of samples. Handle the blank sampling tube

in the same manner as the other samples, except draw no air through it.

2.3.10 Record sample air volumes (in liters) for each sample, along with any potential interferences.

2.3.11 Ship any bulk sample(s) in a container separate from the air samples.

2.3.12 Submit the samples to the laboratory for analysis as soon as possible after sampling. If delay is unavoidable, store the samples at reduced temperature.

2.4 Sampler capacity

Sampler capacity is determined by measuring how much air can be sampled before the analyte breaks through the sampler, i.e., the sampler capacity is exceeded. Breakthrough is considered to occur when the effluent from the sampler contains a concentration of analyte that is 5% of the upstream concentration (5% breakthrough). Testing for breakthrough was performed by using an FID to monitor the effluent from sampling tubes containing only either the 150-mg section of Anasorb CMS or 140-mg section of Anasorb 747. Dynamically generated test atmospheres, which were about two times the higher target concentration of each analyte, were used for the capacity tests. The samples were collected at 0.05 L/min and the relative humidity was about 80% at 25°. The 5% breakthrough air volumes were calculated from the data of duplicate determinations and are listed below. (Section 4.9)

Table 2.4
Sampler Capacity

analyte atmospheric Anasorb Anasorb
concentration CMS 747

enflurane 165 ppm 28.8 L 14.2 L
(1247 mg/m3)
halothane 93 ppm 15.8 L 19.9 L
(753 mg/m3)
isoflurane 165 ppm 24.0 L 17.5 L
(1246 mg/m3)

2.5 Desorption efficiency

2.5.1 The average desorption efficiencies for the analyses from the sampling media over the range of 0.5 to 2.0 times the target concentrations (TC) are listed below. (Section 4.10)

Table 2.5.1
Desorption Efficiencies, %

analyte Anasorb CMS Anasorb 747
low TC high TC low TC high TC

enflurane 100.3 99.8 103.7 100.5
halothane 99.7 99.5 99.6 99.3
isoflurane 99.4 99.2 100.8 100.2

2.5.2 The desorption efficiencies at 0.05, 0.1 and 0.2 times the target concentrations (TC) were found to be very high and are listed below. (Section 4.10)

Table 2.5.2.1
Desorption Efficiencies at 0.05 to 0.2 times Low TC, %

analyte Anasorb CMS Anasorb 747
0.05×Tc 0.1×TC 0.2×TC 0.05×TC 0.1×TC 0.2×TC

enflurane 100.2 100.4 99.5 101.3 99.0 99.0
halothane 99.6 100.5 99.8 84.3 92.6 94.7
isoflurane 99.3 98.4 99.9 96.8 100.0 101.1



Table 2.5.2.2
Desorption Efficiencies at 0.05 to 0.2 times High TC, %

analyte Anasorb CMS Anasorb 747
0.05×TC 0.1×TC 0.2×TC 0.05×TC 0.1×TC 0.2×TC

enflurane 100.1 99.8 99.8 100.2 100.0 100.3
halothane 99.3 98.9 98.5 99.6 98.6 100.4
isoflurane 100.0 99.3 99.2 98.0 97.2 99.0

2.5.3 Desorbed samples remain stable for at least 22.5 h.

2.6 Recommended air volume and sampling rate

2.6.1 For long-term samples, collect 12 L at 0.05 L/min.

2.6.2 For short-term samples, collect 0.75 L at 0.05 L/min.

2.6.3 When short-term samples are collected, the air concentration equivalent to the reliable quantitation limit becomes larger.

Table 2.6.3
Reliable Quantitabon Limits at 0.75 L

adsorbent enflurane halothane isoflurane

Anasorb CMS 2.26 µg 2.36µg 2.08 µg
399 ppb 390 ppb 368 ppb
3013 µg/m3 3147 µg/m3 2773 µg/m3
Anasorb 747 3.68 µg 2.07 µg 2.13 µg
651 ppb 342 ppb 377 ppb
4707 µg/m3 2760 µg/m3 2840 µg/m3

2.7 Interferences (sampling)

2.7.1 It is not known if any compounds will severely interfere with the collection of enflurane, halothane and isoflurane on Anasorb CMS or Anasorb 747. In general, the presence of other contaminant vapors in the air will reduce the capacity of Anasorb CMS or Anasorb 747 to collect the three analyses.

2.7.2 Nitrous oxide was tested as an interferant to the collection of halothane and it does not interfere. (Section 4.12)

2.7.3 Suspected interferences should be reported to the laboratory with submitted samples.

2.8 Safety precautions (sampling)

2.8.1 The sampling equipment should be attached to the worker in such a manner that it will not interfere with work performance or safety.

2.8.2 All safety practices that apply to the work area being sampled should be followed.

2.8.3 Protective eyewear should be worn when breaking the ends of the glass sampling tubes.

3. Analytical Procedure

3.1 Apparatus

3.1.1 Gas chromatograph equipped with an FID. For this evaluation, a Hewlett-Packard 5890A Gas Chromatograph equipped with a 7673A Automatic Sampler was used. A Forma Scientific Model 2006 refrigerated circulator was used to cool the sample tray of the HP 7673A to 10° to minimize evaporation.

3.1.2 A GC column capable of separating the analyte of interest from the desorption solvent, internal standard and any interferences. A 60-m × 0.32-mm i.d. fused silica Stabilwax-D8419 column with a 1-µm df (Restek Corp., Bellefonte, PA) was used in the evaluation.

3.1.3 An electronic integrator or some other suitable means of measuring peak areas. A Waters 860 Networking Computer System was used in this evaluation.

3.1.4 Two-milliliter vials with polytetrafluoroethylene-lined caps.

3.1.5 A dispenser capable of delivering 1.0 mL of desorbing solvent to prepare standards and samples. If a dispenser is not available, a 1.0-mL volumetric pipes may be used.

3.2 Reagents

Enflurane, USP. The enflurane used in this evaluation was manufactured by Anequest (Madison, WI), and purchased from a local hospital.

3.2.2 Halothane, reagent grade or better. The halothane used in this evaluation was purchased from Aldrich Chemical (Milwaukee, WI).

3.2.3 Isoflurane, USP. The isoflurane used in this evaluation was manufactured by Anequest (Madison, WI), and purchased from a local hospital.

3.2.4 Carbon disulfide (CS2), reagent grade or better. The CS2 used in this evaluation was purchased from JT Baker Chemical (Phillipsburg, NJ).

3.2.5 A suitable internal standard, reagent grade. The n-decane used in this evaluation was purchased from ICN Pharmaceuticals, Inc. (Plainview, NY).

3.2.6 Desorption solvent. The desorption solvent contains 500 µL of n-decane per 1 L of CS2.

3.2.7 GC grade nitrogen, air, and hydrogen.

3.2.8 Toluene, chromatographic grade or better. The toluene used in this evaluation was Optima Grade and was purchased from Fisher Scientific (Fair Lawn, NJ).

3.3 Standard preparation

3.3.1 Prepare concentrated stock standard of enflurane, halothane and isoflurane in toluene. Prepare working analytical standards by injecting microliter amounts of concentrated stock standards into 2-mL vials containing 1.0 mL of desorption solvent delivered from the same dispenser used to desorb samples. For example, to prepare a target level standard of isoflurane, inject 10 µL of a stock solution containing 672 mg/mL of isoflurane in toluene into 1 mL of desorption solvent.

3.3.2 Bracket sample concentrations with working standard concentrations. If samples fall outside the concentration range of prepared standards, prepare and analyze additional standards or dilute the sample.

3.4 Sample preparation

3.4.1 Remove the plastic end caps from the sample tube and carefully transfer each section of the adsorbent to separate 2-mL vials. Discard the glass tube, urethane foam plugs and glass wool plug.

3.4.2 Add 1.0 mL of desorption solvent to each vial using the same dispenser as used for preparation of standards.

3.4.3 Immediately seal the vials with polytetrafluoroethylene-lined caps.

3.4.4 Shake the vials vigorously several times during the next 30 min.

3.5 Analysis

3.5.1 Analytical conditions

GC conditions
zone
temperatures:
60° (column)
250° (injector)
300° (detector)
run time: 15 min
column gas flow:     1.2 mL/min (hydrogen)
septum purge: 1.5 mL/min (hydrogen)
injector size: 1.0 µL (11.3:1 split)
column: 60-m × 0.32-mm i.d. capillary Stabilwax-DB (1.0-µm df)
retention times: 5.50 min (isoflurane)
5.97 min (halothane)
6.51 min (enflurane)
8.34 min (n-decane)
FID conditions
hydrogen flow: 34 mL/min
air flow: 450 mL/min
makeup flow: 33 mL/min (nitrogen)

chromatogram

Figure 3.5.1.1. Chromatogram obtained at the high TC with the recommended condibons. Peak identification: (1) carbon disutfide, (2) isoflurane, (3) halothane, (4) enflurane, (5) benzene - contaminant in CS2, (6) n-decane, (7) toluene - from spiking solution.

chromatogram

Figure 3.5.1.2. Chromatogram obtained at the low TC with the recommended conditions. Peak identification: (1) carbon disulfide, (2) isoflurane, (3) halothane, (4) enflurane, (5) benzene - contaminant in CS2, (6) n-decane, (7) toluene - from spiking solution.

3.5.2 An internal standard (ISTD) calibration method is used. A calibration curve can be constructed by plotting micrograms of analyte per sample versus ISTD-corrected response of standard injections. Bracket the samples with freshly prepared analytical standards over a range of concentrations.

graph

Figure 3.5.2.1. Calibrabon curve of enflurane at low TC made from data of Table 4.5.1.

graph

Figure 3.5.2.2. Calibrabon curve of enflurane at high TC made from data of Table 4.5.2.

graph

Figure 3.5.2.3. Calibrabon curve of halothane at low TC made from data of Table 4.5.3.

graph

Figure 3.5.2.4. Calibration curve of halothane at high TC made from data of Table 4.5.4.

graph

Figure 3.5.2.5. Calibration curve of isoflurane at low TC made from data of Table 4.5.5.

graph

Figure 3.5.2.6. Calibration curve of isoflurane at high TC made from data of Table 4.5.6.

3.6 Interferences (analytical)

3.6.1 Any compound that produces an FID response and has a similar retention time as the analyses or internal standard is a potential interference. If any potential interferences were reported, they should be considered before the samples are desorbed.

3.6.2 Generally, chromatographic conditions can be altered to separate an interference from the analyte.

3.6.3 When necessary, the identity or purity of an analyte peak may be confirmed with additional analytical data. (Section 4.11)

3.7 Calculations

The amount of analyte per sampler is obtained from the appropriate calibration curve in terms of micrograms per sample, uncorrected for desorption efficiency. The back (70-75 mg) section is analyzed primarily to determine if there was any breakthrough from the front (140-150 mg) section during sampling. If a significant amount of analyte is found on the back section (e.g., greater than 25% of the amount found on the front section), this fact should be reported with the sample results. If any analyte is found on the back section, it is added to the amount on the front section. This amount is then corrected by subtracting the total amount (if any) found on the blank. The air concentration is calculated using the following formulae.

mg/m3  =  micrograms of analyte per sample
  liters of air sampled × desorption efficiency  


ppm  =  24.46 × mg/m3
  molecular weight of analyte  


where 24.46 is the molar volume at 25° and 101.3 kPa (760 mmHg)
184.49 = molecular weight of enflurane and isoflurane
197.39 = molecular weight of halothane

3.8 Safety precautions (analytical)

3.8.1 Adhere to the rules set down in your Chemical Hygiene Plan.

3.8.2 Avoid skin contact and inhalation of all chemicals.

3.8.3 Wear safety glasses, gloves and a lab coat at all ffmes while in the laboratory areas.

4. Backup Data

4.1 Determination of detection limits

Detection limits, in general, are defined as the amount (or concentration) of analyte that gives a response (YDL) that is significantly different [three standard deviations (SDBR)] from the background response (YBR).

YDL - YBR = 3(SDBR)

The measurement of YBR and SDBR in chromatographic methods is typically inconvenient and difficult because YBR is usually extremely low. Estimates of these parameters can be made with data obtained from the analysis of a series of analytical standards or samples whose responses are in the vicinity of the background response. The regression curve obtained for a plot of instrument response versus concentration of analyte will usually be linear. Assuming SDBR and the precision of the data about curve are similar, the standard error of estimate (SEE) for the regression curve can be substituted for SDBR in the above equation. The following calculations derive a formula for DL:

standard error of estimate

Yobs  =  observed response
Yest  =  estimated response from regression curve
n  =  total number of data points
k  =  2 for linear regression curve

At point YDL on the regression curve

YDL - A(DL) + YBR A = analytical sensitivity (slope)

therefore

DL = (YDL - YBR)
A

Substituting 3(SEE) + YBR for YDL gives

DL = 3(SEE)
A

4.2 Detection limit of the analytical procedure (DW)

The DW is measured as the mass of analyte actually introduced into the chromatographic columns. Ten analytical standards were prepared in equal descending increments with the highest standard containing 10.02, 10.68 and 9.89 µg/mL of enflurane, halothane and isoflurane respecffvely. This is the concentration that would produce a peak approximately 10 times the baseline noise of a reagent blank near the elution time of the analyte. These standards, and the reagent blank, were analyzed with the recommended analytical parameters (1-µL injection with a 11.3:1 split), and the data obtained were used to determine the required parameters (A and SEE) for the calculation of the DLAP.

Table 4.2.1
DLAP Data for Enflurane
A = 3.81 SEE = 117.9

concentration mass on column area counts
(µg/mL) (pg) (µV-s)

0 0 0
0.956 84.4 455
1.90 168 840
2.84 251 1002
3.77 333 1145
5.60 494 2090
6.50 574 2105
7.39 653 2610
8.28 731 2869
9.15 808 3041
10.02 884 3519


graph

Figure 4.2.1 Plot of the data from Table 4.2.1 to determine the DLAP of enflurane, DLAP = 92.8 pg.

Table 4.2.2
DLAP Data for Halothane
A = 4.08 SEE = 118.7

concentration mass on column area counts
(µg/mL) (pg) (µV-s)

0 0 0
1.02 90 413
2.03 179 916
3.03 267 1219
5.97 527 2366
6.93 612 2501
7.88 696 2907
8.82 779 3219
9.76 861 3416
10.68 943 4035


graph

Figure 4.2.2. Plot of the data from Table 4.2.2 to determine the DW of halothane, DLAP = 87.3 pg.

Table 4.2.3
DLAP Data for Isoflurane
A = 2.34 SEE = 34.90

concentration mass on column area counts
(µg/mL) (pg) (µV-s)

0 0 0
0.944 83 288
1.88 166 421
2.80 247 627
3.72 328 794
5.53 488 1230
6.41 566 1307
7.30 644 1537
8.17 721 1711
9.03 797 1921
9.89 873 2090


graph

Figure 4.2.3 Plot of the data from Table 4.2.3 to determine the DLAP of isoflurane, DLAP = 44.7 pg.

4.3 Detection limit of the overall procedure (DLOP)

The DLOP is measured as mass per sample and expressed as equivalent air concentration, based on the recommended sampling parameters. Ten samplers were spiked with equal descending increments of analyte, such that the highest sampler loading was 9.15, 9.76 and 9.03 µg/sample of enflurane, halothane and isoflurane respectively. This is the amount, when spiked on a sampler, that would produce a peak approximately 10 times the baseline noise for a sample blank. These spiked samplers, plus a sample blank, were analyzed with the recommended analytical parameters, and the data obtained used to calculate the required parameters (A and SEE) for the calculation of the DLOP.

Table 4.3.1
DLOP Data for Enflurane

mass per area counts on area counts on
sample Anasorb CMS Anasorb 747
(µg) (µV-s) (µV-s)

0.956 441 292
1.90 651 735
2.84 1042 1109
3.77 1423 1449
4.69 1618 1690
5.60 1858 1786
6.50 2084 2430
7.39 2378 2393
8.28 2635 2749
9.15 3035 3238


graph

Figure 4.3.1.1. Plot of the data to determine the DLOP of enflurane on Anasorb CMS, (SEE = 71.55).

graph

Figure 4.3.1.2. Plot of the data to determine the DLOP of enflurane on Anasorb 747, (SEE = 124.5).

Table 4.3.2
DLOP Data for Halothane

mass per area counts on area counts on
sample Anasorb CMS Anasorb 747
(µg) (µV-s) (µV-s)

0 0 0
1.02 512 382
2.03 761 812
3.03 1224 1263
4.02 1554 1670
5.00 1870 1999
5.97 2192 2481
6.93 2526 2795
7.88 2721 3059
8.82 3288 3319
9.76 3677 3761


graph

Figure 4.3.2.1. Plot of the data to determine the DLOP of halothane on Anasorb CMS, (SEE = 85.02).

graph

Figure 4.3.2.2 Plot of the data to determine the DLOP of halothane on Anasorb 747, (SEE = 79.37).

Table 4.3.3
DLOP Data for Isodurane

mass per area counts on area counts on
sample Anasorb CMS Anasorb 747
(µg) (µV-s) (µV-s)

0 0 0
0.944 274 245
1.88 444 442
2.80 654 630
3.72 845 813
4.63 963 1041
5.53 1195 1088
6.41 1349 1326
7.30 1564 1488
8.17 1622 1615
9.03 1877 1825


graph

Figure 4.3.3.1. Plot of the data to determine the DLOP of isoflurane on Anasorb CMS, (SEE = 41.65).

graph

Figure 4.3.3.2. Plot of the data to determine the DLOP of isoflurane on Anasorb 747, (SEE = 41.51).

4.4 Reliable quantitation limit (RQL)

The RQL is considered the lower limit for precise quantitative measurements. It is determined from the regression line parameters obtained for the calculations of the DLOP (Section 4.3), providing at least 75% of the analyte is recovered. The RQL is defined as the amount of analyte that gives a response (YRQL) such that

YRQL - YBR = 10(SDBR)

therefore

RQL  =   10(SEE)
A

chromatogram

Figure 4.4.1. Chromatogram of the RQL for all three analyses on Anasorb CMS.

chromatogram

Figure 4.4.2. Chromatogram of the RQL for halothane and isoflurane on Anasorb 747.

chromatogram

Figure 4.4.3. Chromatogram of the RQL for enflurane on Anasorb 747.

Table 4.4
Reliable Quantitation Limits

adsorbent enflurane halothane isoflurane

Anasorb CMS 2.26 µg 2.36 µg 9 2.08 µg
225 ppb 219 ppb 207 ppb
1695 µg/m3 1770 µg/m3 1560µg/m3
91.7% 95.9% 104.1%
Anasorb 747 3.68 µg 2.07 µg 2.13 µg
366 ppb 192 ppb 212 ppb
2760 µg/m3 1553 µg/m3 1598 µg/m3
109.2% 102.9% 103.6%

The RQL for each analyte was calculated and listed above along with the recovery of the analyte peak near the RQL.

4.5 Precision (analytical method)

The precision of the analytical procedure is measured as the pooled relative standard deviation (RSDP). Relative standard deviations are determined from six replicate injections of analyte standards at 0.5, 0.75, 1, 1.5 and 2 times the target concentration. After assuring that the RSDs satisfy the Cochran test for homogeneity at the 95% confidence level, RSDP was calculated.

Table 4.5.1
Instrument Response to Enflurane at Low TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 45.6 68.4 91.2 136.8 182.4

area counts 5802 8044 11502 15685 21003
(µV-s) 5762 7971 11748 15514 20685
5592 8178 11513 15995 19527
5604 8024 10887 16911 20585
5898 8173 11441 15579 19114
5902 8146 11336 15502 19871
mean 5760 8089 11405 15864 20131
SD 136.8 87.6 287.4 544.1 740.3
RSD (%) 2.37 1.08 2.52 3.42 3.67



Table 4.5.2
Instrument Response to Enflurane at High TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 3405 5108 6810 10215 13620

area counts 313768 442725 588885 909618 1266303
(µV-s) 295385 449118 614061 884040 1231585
306119 444388 600184 888369 1239847
302927 452003 605174 873998 1195472
302101 463954 583097 872158 1232590
315239 450679 623083 934700 1220325
mean 305923 450478 602414 893814 1231020
SD 7523.3 7523.5 15044.1 24117.5 23253.5
RSD (%) 2.45 1.67 2.48 2.69 1.88



Table 4.5.3
Instrument Response to Halothane at Low TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 48.62 72.93 97.24 145.9 194.5

area counts 4652 6892 9563 14067 19459
(µV-s) 4572 6936 9438 14324 18888
4781 6802 9773 14181 18732
4625 6931 9501 14180 19216
4630 6802 9694 14534 18964
4609 6960 9404 14271 19499
mean 4645 6887 9562 14260 19126
SD 71.8 69.5 145.6 160.7 315.0
RSD (%) 1.54 1.00 1.52 1.12 1.64



Table 4.5.4
Instrument Response to Halothane at High TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 2431 3646 4862 7293 9724

area counts 214963 31920 427008 631533 876733
(µV-s) 211987 326882 426550 625176 856581
218236 322866 430225 620733 870877
215433 325338 429946 632545 849740
214585 329467 436427 647793 860103
207597 319337 433215 623791 847012
mean 213800 323849 430562 630262 860174
SD 3635.3 4144.4 3759.2 9723.2 11694.2
RSD (%) 1.70 1.27 0.87 1.54 1.35



Table 4.5.5
Instrument Response to Isoflurane at Low TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 45.0 67.5 90.0 135.0 180.0

area counts 3164 4584 6793 9544 14068
(µV-s) 3083 4690 6928 9750 13672
3239 4700 6791 10564 13408
2983 4510 6209 10076 12670
3120 4546 6809 9707 13257
3147 4757 6621 9820 12437
mean 3123 4631 6692 9910 13252
SD 85.9 98.2 256.0 364.5 611.5
RSD (%) 2.75 2.11 3.82 3.67 4.61



Table 4.5.6
Instrument Response to Isoflurane at High TC

× target concn 0.5× 0.75× 1.5×
(µg/mL) 3360 5040 6720 10080 13440

area counts 192010 285648 377707 560192 831803
(µV-s) 198666 302263 389365 536323 808032
196337 286004 390013 576197 832183
197101 283263 392882 581411 807540
184540 294184 416447 572522 811381
202374 287224 410104 564809 803188
mean 95171 289764 396086 565242 815688
SD 6199.9 7149.2 14430.4 16102.5 12896.4
RSD (%) 3.17 2.46 3.64 2.84 1.58



The Cochran test for homogeneity:

formula for Cochran test for homogeneity

The critical value of the g-statistic, at the 95% confidence level, for five variances, each associated with six observations is 0.5065. Because the g-statistic does not exceed this value, the RSDs can be considered equal and they can be pooled (RSDP) to give an estimated RSD for the concentration range studied.

Table 4.5.7
Cochran Test Results and Pooled Relative Standard Deviations

enflurane halothane isoflurane

TC low high low high low high
g 0.3515 0.2808 0.2785 0.3058 0.3465 0.3317
RSDP % 2.77 2.27 1.39 1.37 3.50 2.83

4.6 Precision (overall procedure)

The precision of the overall procedure is determined from the storage data in Section 4.7. The determination of the standard error of estmate (SEER) for a regression line ptotted through the graphed storage data allows the inclusion of storage time as one of the factors affecting overall precision. The SEER is similar to the standard deviation, except it is a measure of the dispersion of data about a regression line instead of about a mean. It is determined with the following equation:

formula for standard error of estimate for a regression line

Yobs = observed % recovery at a given time
Yest = estimated % recovery from the regression line at the same given time
n = total number of data points
k = 2 for linear regression
k = 3 for quadratic regression

An additional 5% for pump error (SP) is added to the SEER by the addition of variances to obtain the total standard error of the estimate.

The precision at the 95% confidence level is obtained by multiplying the standard error of estimate (with pump error included) by 1.96 (the z-statistic from the standard normal distribution at the 95% confidence level). The 95% confidence intervals are drawn about their respective regression lines in the storage graphs, as shown in figures 4.7.1.1.1 through 4.7.2.6.2. The precisions of the overall procedure and the assodated figures are listed below.

Table 4.6.1
Precision of the Overall Procedure on Anasorb CMS, %

target concn enflurane halothane isoflurane

1 ppm 14.1 14.9 15.3
Fig. 4.7.2.1.1 Fig. 4.7.2.3.2 Fig. 4.7.2.5.1
50 ppm 13.7
Fig 4.7.1.3.1
75 ppm 16.3 16.6
Fig. 4.7.1.1.1 Fig. 4.7.1.5.1



Table 4.6.2
Precision of the Overall Procedure on Anasorb 747, %

target concn enflurane halothane isoflurane

1 ppm 11.3 10.6 11.5
Fig. 4.7.2.2.1 Fig. 4.7.2.4.1 Fig. 4.7.2.6.1
50 ppm 11.4
Fig. 4.7.1.4.1
75 ppm 15.1 12.0
Fig. 4.7.1.2.1 Fig. 4.7.1.6.1

4.7 Storage test

4.7.1 Analyte storage at high target concentration

4.7.1.1 Storage samples were generated by sampling from a controlled test atmosphere containing 2120 mg/m3 of enflurane, about 3.7 times the 75-ppm target concentration. Anasorb CMS tubes were used to sample for 60 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.1
Storage Test for Enflurane on Anasorb CMS

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 90.0 101.5 98.0 90.0 101.5 98.0
101.9 103.4 95.3 101.9 103.5 95.3
3 101.0 101.6 94.6 90.9 88.3 95.6
6 102.1 105.1 107.3 111.1 103.6 98.7
9 101.8 104.1 95.4 90.7 97.0 100.5
13 97.8 88.4 91.9 98.3 112.7 103.3
15 91.1 102.7 90.7 92.0 100.2 102.3


graph

Figure 4.7.1.1.1. Ambient storage test for enflurane on Anasorb CMS.

graph

Figure 4.7.1.1.2. Refrigerated storage test for enflurane on Anasorb CMS.

4.7.1.2 Storage samples were generated by sampling from a controlled test atmosphere containing 2118 mg/m3 of enflurane, about 3.7 times the 75-ppm target concentration. Anasorb 747 tubes were used to sample for 60 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.2
Storage Test for Enflurane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 96.3 97.4 106.9 96.3 97.4 106.9
102.1 101.7 102.5 102.1 101.7 102.5
2 92.4 84.7 100.8 96.9 101.4 98.2
6 92.0 104.1 97.6 95.1 96.9 99.6
9 102.2 96.7 106.3 93.1 104.2 99.0
12 97.2 112.2 105.2 102.1 103.0 105.6
16 102.0 102.6 105.7 99.1 112.2 106.9



graph

Figure 4.7.1.2.1 Ambient storage test for enflurane on Anasorb 747.

graph

Figure 4.7.1.2.2. Refrigerated storage test for enflurane on Anasorb 747.

4.7.1.3 Storage samples were generated by sampling from a controlled test atmosphere containing 2146 mg/m3 of halothane, about 5.3 times the 50-ppm target concentration. Anasorb CMS tubes were used to sample for 60 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stared at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 24 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.3
Storage Test for Halothane on Anasorb CMS

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 103.3 104.3 90.8 103.3 104.3 90.8
98.3 95.5 98.7 98.3 95.5 98.7
4 101.5 95.4 96.9 106.6 91.4 99.6
6 103.2 88.7 96.0 99.1 95.8 98.8
8 103.5 101.1 97.7 108.3 92.9 100.4
12 106.0 91.0 94.5 108.7 102.0 102.3
15 96.06 91.1 93.6 103.6 90.6 101.1

graph

Figure 4.7.1.3.1. Ambient storage test for halothane on Anasorb CMS.

graph

Figure 4.7.1.3.2. Refrigerated storage test for halothane on Anasorb CMS

4.7.1.4 Storage samples were generated by sampling from a controlled test atmosphere containing 2305 mg/m3 of halothane, about 5.7 times the 50-ppm target concentration. Anasorb 747 tubes were used to sample for 60 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 3-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.4
Storage Test for Halothane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery(%)

0 99.1 100.0 103.9 99.1 100.0 103.9
100.5 99.7 96.9 100.5 99.7 96.9
3 99.4 99.2 96.2 98.6 104.2 98.9
6 98.8 104.2 98.8 101.5 100.1 97.3
10 99.1 103.5 94.9 100.9 105.0 101.3
13 95.8 104.5 98.7 101.3 95.7 95.5
17 103.8 104.8 99.6 102.7 105.9 99.2


graph

Figure 4.7.1.4.1. Ambient storage test for halothane on Anasorb 747.

graph

Figure 4.7.1.4.2. Refrigerated storage test for halothane on Anasorb 747.

4.7.1.5 Storage samples were generated by sampling from a controlled test atmosphere containing 3050 mg/m3 of isoflurane, about 5.4 times the 75-ppm target concentration. Anasorb CMS tubes were used to sample for 60 min at 0.05 L/min the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.5
Storage Test for Isoflurane on Anasorb CMS

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 99.7 103.6 93.9 99.7 103.6 93.6
99.0 85.4 97.8 99.0 85.4 97.8
4 111.9 104.8 97.5 106.7 91.7 92.1
7 99.2 94.2 90.2 108.8 103.0 100.6
11 113.1 102.9 102.3 106.5 99.1 91.4
13 103.9 96.4 92.0 108.0 105.3 103.6
15 108.0 105.1 106.1 105.0 100.3 96.8


graph

Figure 4.7.1.5.1. Ambient storage test for isoflurane on Anasorb CMS.

graph

Figure 4.7.1.5.2. Refrigerated storage test for isoflurane on Anasorb CMS.

4.7.1.6 Storage samples were generated by sampling from a controlled test atmosphere containing 2992 mg/m3 of isoflurane, about 5.3 times the 75-ppm target concentration. Anasorb 747 tubes were used to sample for 60 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a dosed drawer at ambient temperature (about 22°). At 3-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.1.6
Storage Test for Isoflurane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 92.3 99.3 99.1 92.3 99.3 99.1
99.6 100.6 101.5 99.6 100.6 101.5
4 99.6 97.4 102.6 97.0 92.1 98.2
7 92.5 94.9 101.0 103.2 102.8 103.5
10 100.5 103.2 102.5 98.0 97.0 100.7
14 103.1 100.6 108.3 106.8 102.4 105.9
18 107.7 100.1 105.1 103.1 100.5 104.1



graph

Figure 4.7.1.6.1. Ambient storage test for isoflurane on Anasorb 747.

graph

Figure 4.7.1.6.2. Refrigerated storage test for isoflurane on Anasorb 747.

4.7.2 Analyte storage at low target concentration

4.7.2.1 Storage samples were generated by sampling from a controlled test atmosphere containing 58.2 mg/m3 of enflurane, about 7.7 times the 1-ppm target concentration. Anasorb CMS tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.1

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 82.6 88.7 94.1 82.6 88.7 94.1
98.8 98.3 102.9 98.8 98.3 102.9
4 90.1 92.9 97.0 90.4 101.0 101.7
7 91.6 99.9 102.2 96.6 103.9 99.0
11 99.1 96.6 100.9 90.0 100.8 96.9
13 88.3 95.9 97.3 104.9 97.7 98.1
15 96.3 92.1 95.6 86.6 93.0 102.0



graph

Figure 4.7.2.1.1. Ambient storage test for enflurane on Anasorb CMS.

graph

Figure 4.7.2.1.2. Refrigerated storage test for enflurane on Anasorb CMS.

4.7.2.2 Storage samples were generated by sampling from a controlled test atmosphere containing 59.4 mg/m3 of enflurane, about 7.9 times the 1-ppm target concentration. Anasorb 747 tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-6 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.2
Storage Test for Enflurane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 101.8 93.4 96.5 101.8 93.4 96.5
100.0 103.4 98.3 100.0 103.4 98.3
3 102.3 98.9 97.3 99.0 96.3 101.1
6 101.7 104.0 102.9 98.8 101.8 100.3
12 98.3 100.2 96.4 98.0 98.2 101.3
14 101.1 101.3 102.7 102.2 104.2 96.7
18 98.6 99.0 95.8 106.9 100.7 103.0



graph

Figure 4.7.2.2.1. Ambient storage test for enflurane on Anasorb 747.


graph

Figure 4.7.2.2.2. Refrigerated storage test for enflurane on Anasorb 747.

4.7.2.3 Storage samples were generated by sampling from a controlled test atmosphere containing 70.1 mg/m3 of halothane, about 8.7 times the 1-ppm target concentration. Anasorb CMS tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-5 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.3
Storage Test for Halothane on Anasorb CMS

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 91.7 93.8 98.7 91.7 93.8 98.7
101.1 103.6 106.9 101.1 103.6 106.9
3 80.6 88.4 95.5 89.3 95.4 105.5
8 78.8 85.6 90.1 92.6 99.3 100.5
12 79.2 85.3 92.4 86.5 107.4 100.0
14 77.2 86.9 98.0 97.0 98.6 101.2
16 73.4 80.0 92.0 92.5 94.4 100.2



graph

Figure 4.7.2.3.1. Ambient storage test for halothane on Anasorb CMS.


graph

Figure 4.7.2.3.2. Refrigerated storage test for halothane on Anasorb CMS.

4.7.2.4 Storage samples were generated by sampling from a controlled test atmosphere containing 71.2 mg/m3 of halothane, about 8.8 times the 1-ppm target concentration. Anasorb 747 tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-4 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.4
Storage Test for Halothane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 97.8 104.5 97.5 97.8 104.5 97.5
99.4 101.0 99.8 99.4 101.0 99.8
3 99.2 102.0 98.0 97.3 99.0 103.4
6 - 100.2 100.8 98.4 105.3 97.1
9 104.5 103.7 101.0 98.9 111.2 102.6
13 101.0 102.7 100.6 106.0 102.3 99.7
15 105.7 103.0 101.4 113.3 101.0 101.1



graph

Figure 4.7.2.4.1. Ambient storage test for halothane on Anasorb 747.


graph

Figure 4.7.2.4.2. Refrigerated storage test for halothane on Anasorb 747.

4.7.2.5 Storage samples were generated by sampling from a controlled test atmosphere containing 50.4 mg/m3 of isoflurane, about 6.7 times the 1-ppm target concentration. Anasorb CMS tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 24 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.5
Storage Test for Isoflurane on Anasorb CMS

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 79.1 88.1 91.8 79.1 88.1 91.8
  98.9 98.0 103.2 98.9 98.0 103.2
4 97.8 96.5 101.7 90.7 101.8 105.7
7 91.5 97.4 102.2 94.5 103.7 100.8
11 97.6 94.0 98.7 89.3 102.3 100.0
13 85.4 95.1 98.0 105.3 98.9 96.1
15 92.1 87.4 92.7 85.0 89.4 99.4



graph

Figure 4.7.2.5.1. Ambient storage test for isonurane on Anasorb CMS.


graph

Figure 4.7.2.5.2. Refrigerated storage test for isoflurane on Anasorb CMS.

4.7.2.6 Storage samples were generated by sampling from a controlled test atmosphere containing 52.7 mg/m3 of isoflurane, about 7 times the 1-ppm target concentration. Anasorb 747 tubes were used to sample for 30 min at 0.05 L/min, the relative humidity was about 80% at 22°. Thirty-six storage samples were prepared. Six samples were analyzed immediately after generation, fifteen tubes were stored at reduced temperature (4°) and the other fifteen were stored in a closed drawer at ambient temperature (about 22°). At 2-6 day intervals, three samples were selected from each of the two sets and analyzed.

Table 4.7.2.6
Storage Test for Isoflurane on Anasorb 747

time ambient storage refrigerated storage
(days) recovery (%) recovery (%)

0 102.3 90.5 96.7 102.3 90.5 96.7
100.0 104.2 96.8 100.0 104.2 96.8
3 101.8 98.0 98.4 100.7 97.4 102.0
6 102.5 102.6 101.2 98.4 102.3 100.6
12 97.7 98.5 96.7 99.9 100.5 102.3
14 99.5 99.5 100.9 102.8 101.6 96.0
16 98.4 96.9 97.0 107.6 101.8 103.2



graph

Figure 4.7.2.6.1. Ambient storage test for isoflurane on Anasorb 747.


graph

Figure 4.7.2.6.2. Refrigerated storage test for isoflurane on Anasorb 747.

4.8 Reproducibility

4.8.1 Analyte reproducibility at high target concentration

4.8.1.1 Six samples for each adsorbent were prepared by collecting them from a 75-ppm controlled test atmosphere containing enflurane and isoflurane for 4 h at 0.05 L/min. The samples were submitted to an OSHA Salt Lake Technical Center service branch. The samples were analyzed after being stored for 21 days at 4°. Sample results were corrected for desorption efficiency. No sample result for enflurane or isoflurane had a deviation greater than the precision of the overall procedure determined in Section 4.6.

Table 4.8.1.1.1
Reproducibility Data for Enflurane

Anasorb CMS Anasorb 747
sample expected reported recovery deviation reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 570 546.3 95.9 -4.1 517.6 90.8 -9.2
2 570 517.3 90.9 -9.1 533.1 93.5 -6.5
3 570 544.1 95.5 -4.5 520.3 91.3 -8.7
4 570 556.9 97.7 -2.3 532.1 93.4 -6.6
5 570 518.7 91.0 -9.0 499.6 87.7 -12.3
6 570 536.9 94.2 -5.8 524.0 91.9 -8.1



Table 4.8.1.1.2
Reproducibility Data for Isoflurane

Anasorb CMS Anasorb 747
sample expected reported recovery deviabon reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 562.5 596.6 106.1 +6.1 562.3 100.0 0
2 562.5 550.2 97.8 -2.2 576.6 102.5 +2.5
3 562.5 591.1 105.1 +5.1 564.0 100.3 +0.3
4 562.5 609.0 108.3 +8.3 578.1 102.8 +2.8
5 562.5 564.8 100.3 +0.3 540.3 96.1 -3.9
6 562.5 587.4 104.4 +4.4 569.2 101.2 1.2

4.8.1.2 Six samples for each adsorbent were prepared by collecting them from a 50-ppm controlled test atmosphere containing halothane for 4 h at 0.05 L/min. The samples were submilted to an OSHA Salt Lake Technical Center service branch. The samples were analyzed after being stored for 17 days at 4°. Sample results were corrected for desorption efficiency. No sample result for halothane had a deviation greater than the precision of the overall procedure determined in Section 4.6.

Table 4.8.1.2
Reproducibility Data for Halothane

Anasorb CMS Anasorb 747
sample expected reported recovery deviation reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 408 411.0 100.7 +0.7 406.2 99.6 -0.4
2 408 406.6 99.7 -0.3 411.1 100.8 +0.8
3 408 402.8 98.7 -1.3 411.5 100.8 +0.8
4 408 409.8 100.4 +0.4 410.6 100.6 +0.6
5 408 399.7 98.0 -2.0 401.7 98.5 -1.5
6 408 406.4 99.6 -0.4 408.1 100.0 0

4.8.2 Analyte reproducibility at low target concentration

4.8.2.1 Six samples for each adsorbent were prepared by collecting them from a 1-ppm controlled test atmosphere containing enflurane and isoflurane for 4 h at 0.05 L/min. The samples were submitted to an OSHA Salt Lake Technical Center service branch. The samples were analyzed after being stored for 22 days at 4°. Sample results were corrected for desorption efficiency. No sample result for enflurane and isoflurane had a deviation greater than the precision of the overall procedure determined in Section 4.6.

Table 4.8.2.1.1
Reproducibility Data for Enflurane

Anasorb CMS Anasorb 747
sample expected reported recovery deviation reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 7.62 8.02 105.2 +5.2 7.81 102.5 +2.5
2 7.62 7.58 99.5 -0.5 7.82 102.6 +2.6
3 7.62 7.62 100.0 0 7.82 102.6 +2.6
4 7.62 6.55 86.0 -14.0 6.95 91.2 -8.8
5 7.62 7.58 99.5 -0.5 7.73 101.4 +1.4
6 7.62 7.65 100.4 +0.4 8.48 111.3 +11.3



Table 4.8.2.3
Reproducibility Data for Isoflurane

Anasorb CMS Anasorb 747
sample expected reported recovery deviation reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 7.52 7.74 102.9 +2.9 7.91 105.2 +5.2
2 7.52 7.47 99.3 -0.7 8.22 109.3 +9.3
3 7.52 7.65 101.7 +1.7 8.32 110.6 +10.6
4 7.52 6.58 87.5 -12.5 7.09 94.3 -5.7
5 7.52 7.15 95.1 -4.9 8.22 109.3 +9.3
6 7.52 7.59 100.9 +0.9 7.70 102.4 +2.4

4.8.2.2 Six samples for each adsorbent were prepared by collecting them from a 1-ppm controlled test atmosphere containing halothane for 4 h at 0.05 L/min. The samples were submitted to an OSHA Salt Lake Technical Center service branch. The samples were analyzed after being stored for 23 days at 4°. Sample results were corrected for desorption efficiency. No sample result for halothane had a deviation greater than the precision of the overall procedure determined in Section 4.6.

Table 4.8.2.2
Reproducibility Data for Halothane

Anasorb CMS Anasorb 747
sample expected reported recovery deviation reported recovery deviation
(mg/m3) (mg/m3) (%) (%) (mg/m3) (%) (%)

1 8.40 7.38 37.9 -12.1 8.79 104.6 +4.6
2 8.40 7.80 92.9 -7.1 8.53 101.5 +1.5
3 8.40 8.32 99.0 -1.0 9.03 107.5 +7.5
4 8.40 7.93 94.4 -5.6 8.81 104.9 +4.9
5 8.40 8.20 97.6 -2.4 8.70 103.6 +3.6
6 8.40 8.67 103.2 +3.2 8.93 106.3 +6.3

4.9 Sampler capacity

4.9.1 Anasorb CMS

4.9.1.1 The sampling capacity of the front section of an Anasorb CMS sampling tube was tested by sampling from a dynamically generated test atmosphere of enflurane (1247 mg/m3 or 165 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 150-mg front test section. The valve was rotated to measure the amount of enflurane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 28.8 L.

Table 4.9.1.1
Capacity of Enflurane on Anasorb CMS

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

17.54 0 16.39 0
18.24 0.79 17.11 0.27
19.62 1.57 20.76 0.69
21.93 2.07 20.97 1.04
23.18 2.50 22.18 1.34
24.19 2.87 22.90 1.57
25.06 3.23 24.20 1.98
26.12 3.93 25.55 2.38
26.99 4.41 26.46 2.83
28.48 5.03 27.57 3.33
29.23 5.59 27.72 3.81
29.99 6.25 28.44 4.24



graph

Figure 4.9.1.1. Five percent breakthrough air volume for enflurane on Anasorb CMS.

4.9.1.2 The sampling capacity of the front section of an Anasorb CMS sampling tube was tested by sampling from a dynamically generated test atmosphere of halothane (753 mg/m3 or 93.3 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 150-mg front test section. The valve was rotated to measure the amount of halothane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 15.8 L.

Table 4.9.1.2
Capacity of Halothane on Anasorb CMS

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

5.88 0 6.06 0
7.10 0 7.26 0
8.37 0 8.52 0
12.42 3.11 12.53 3.08
12.93 3.28 13.03 3.21
13.44 3.71 13.53 3.65
13.94 4.11 14.03 4.00
14.55 4.53 14.63 4.29
15.06 4.64 15.13 4.47
15.56 4.97 15.63 4.72
16.07 5.26 16.13 4.96
16.58 5.74 16.63 5.19
17.09 5.83 17.73 5.58
17.59 6.24 17.64 5.87
18.10 6.32



graph

Figure 4.9.1.2. Five percent breakthrough air volume for haothane on Anasorb CMS.

4.9.1.3 The sampling capacity of the front section of an Anasorb CMS sampling tube was tested by sampling from a dynamically generated test atmosphere of isoflurane (1246 mg/m3 or 165 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 150-mg front test sector. The valve was rotated to measure the amount of isoflurane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 24.0 L.

Table 4.9.1.3
Capacity of Isoflurane on Anasorb CMS

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

9.10 0 10.10 0
13.48 0.42 14.11 0.96
14.51 0.73 15.12 1.42
15.50 1.03 16.13 1.76
16.48 1.39 17.14 1.96
17.76 1.75 18.50 2.42
19.19 2.36 20.06 3.15
20.41 2.86 21.17 3.74
21.50 3.24 22.27 4.24
22.68 3.67 23.49 5.21
23.86 4.32 24.70 6.16
24.85 4.65 25.70 6.89



graph

Figure 4.9.1.3. Five percent breakthrough air volume for isoflurane on Anasorb CMS.

4.9.2 Anasorb 747

4.9.2.1 The sampling capacity of the front section of an Anasorb 747 sampling tube was tested by sampling from a dynamically generated test atmosphere of enflurane (1247 mg/m3 or 165 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 140-mg front test section. The valve was rotated to measure the amount of enflurane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 14.2 L.

Table 4.9.2.1
Capacity of Enflurane on Anasorb 747

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

9.85 0 10.10 0
13.13 1.40 13.43 2.22
13.69 3.12 13.94 3.98
14.24 5.61 14.49 6.29
14.75 7.77 15.00 8.12
15.25 9.13 15.50 9.95



graph

Figure 4.9.2.1. Five percent breakthrough air volume for enflurane on Anasorb 747.

4.9.2.2 The sampling capacity of the front section of an Anasorb 747 sampling tube was tested by sampling from a dynamically generated test atmosphere of halothane (753 mg/m3 or 93.3 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 140-mg front test section. The valve was rotated to measure the amount of halothane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 19.9 L.

Table 4.9.2.2
Capacity of Halothane on Anasorb 747

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

16.07 0 16.13 0
17.34 0 17.38 0
18.86 0.52 18.89 0.45
19.87 2.56 19.94 2.37
20.18 5.06 20.19 4.86
20.43 8.67 20.44 8.70
20.69 12.58 20.69 12.70



graph

Figure 4.9.2.2. Five percent breakthrough air volume for halothane on Anasorb 747.

4.9.2.3 The sampling capacity of the front section of an Anasorb 747 sampling tube was tested by sampling from a dynamically generated test atmosphere of isoflurane (1246 mg/m3 or 165 ppm). The samples were collected at 0.05 L/min and the relative humidity was about 80% at 22°. A GC with a gas sampling valve was placed in-line behind the 140-mg front test section. The valve was rotated to measure the amount of isoflurane passing through the sampler at the time of rotation. The 5% breakthrough air volume was determined to be 17.5 L.

Table 4.9.2.3
Capacity of Isoflurane on Anasorb 747

first test second test
air volume breakthrough air volume breakthrough
(L) (%) (L) (%)

11.21 0 10.66 0
12.20 0 11.62 0
13.20 0.18 12.68 0.12
13.94 0.35 13.64 0.61
14.44 0.59 14.39 1.12
14.94 0.93 14.90 1.59
15.44 1.36 15.40 2.13
15.94 1.94 15.91 2.86
16.43 2.50 16.41 3.72
16.93 3.29 16.92 4.62
17.43 4.07 17.42 5.56
17.93 4.85 17.93 6.69
18.43 5.73 18.43 7.69
18.94 8.76



graph

Figure 4.9.2.3 Five percent breakthrough air volume for isoflurane on Anasorb 747.

4.10 Desorption efficiency and stability of desorbed samples

4.10.1 Anasorb CMS at high target concentration (TC)

4.10.1.1 Enflurane

The desorption efficiencies (DE) of enflurane were determined by liquid-spiking150 mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 75-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption emciency over the working range of 0.5 to 2 times the target concentration is 99.8%.

Table 4.10.1.1.1
Desorbtion Efficiency of Enflurane from Anasorb CMS at High TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 340.5 681 1362 3403 6810 13620

DE (%) 101.4 98.5 100.2 100.2 99.8 99.3
98.7 98.3 97.2 99.6 98.2 98.9
100.5 100.3 100.1 99.9 100.6 98.9
98.9 100.7 101.6 101.2 100.7 100.1
100.8 100.0 99.6 100.3 99.7 97.8
100.1 100.7 100.2 101.0 101.0 99.2
mean 100.1 99.8 99.8 100.4 100.0 99.0

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after intial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -2.0% for samples that were resealed with new septa, and -4.2% for those that retained their punctured septa.

Table 4.10.1.1.2
Stability of Desorbed Samples for Enflurane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

99.8 97.3 -2.5 100.7 98.7 -2.0
98.2 96.7 -1.5 99.7 95.4 -4.3
100.6 98.6 -2.0 101.0 94.8 -6.2
(averages) (averages)
99.5 97.5 -2.0 100.5 96.3 -4.2

4.10.1.2. Halothane

The desorption efficiencies (DE) of halothane were determined by liquid-spiking 150-mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 50-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.5%.

Table 4.10.1.2.1
Desorption Efficiency of Halothane from Anasorb CMS at High TC

×target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 243.1 486.2 972.4 2431 4862 9724

DE (%) 99.4 98.6 98.9 99.1 99.8 99.6
99.6 98.5 96.5 98.8 98.0 99.9
97.4 99.1 98.5 101.8 100.0 99.4
101.0 99.3 99.5 99.6 99.7 100.1
99.0 98.9 98.3 99.5 99.2 98.6
99.2 99.0 99.1 99.8 99.9 98.5
mean 99.3 98.9 98.5 99.8 99.4 99.4

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -1.5% for samples that were resealed with new septa, and -3.4% for those that retained their punctured septa.

Table 4.10.1.2.2
Stability of Desorbed Samples for Halothane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

99.8 97.4 -2.4 99.7 97.7 -2.0
98.0 97.1 -0.9 99.2 96.1 -3.1
100.0 98.8 -1.2 99.9 94.8 -5.1
(averages) (averages)
99.3 97.8 -1.5 99.6 96.2 -3.4

4.10.1.3 Isoflurane

The desorption efficiencies (DE) of isoflurane were determined by liquid-spiking 150-mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 75-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.2%.

Table 4.10.1.3.1
Desorption Efficiency of Isoflurane from Anasorb CMS at High TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 336 672 1344 3360 6720 13440

DE (%) 100.2 97.3 99.6 99.8 99.1 97.6
99.2 99.3 99.4 99.3 97.6 97.3
98.7 99.9 100.9 99.4 99.7 97.8
101.3 100.2 99.3 100.7 99.7 98.5
100.9 99.1 99.5 100.2 103.3 96.8
99.9 99.9 96.5 100.8 99.5 98.1
mean 100.0 99.3 99.2 100.0 99.8 97.7

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -2.3% for samples that were resealed with new septa, and -4.1% for those that retained their punctured septa.

Table 4.10.1.3.2
Stability of Desorbed Samples for Isoflurane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

99.1 96.2 -2.9 99.7 98.0 -1.7
97.6 95.5 -2.1 103.3 98.1 -5.2
99.7 97.8 -1.9 99.5 93.9 -5.4
(averages) (averages)
98.8 96.5 -2.3 100.8 96.7 -4.1

4.10.2 Anasorb 747 at high target concentration (TC)

4.10.2.1 Enflurane

The desorption efficiencies (DE) of.enflurane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the75-ppm target cocentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 100.5%.

Table 4.10.2.1.1
Desorption Effidency of Enflurane from Anasorb 747 at High TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 340.5 681 1362 3405 6810 13620

DE (%) 100.9 100.6 101.4 98.9 103.9 99.5
99.1 99.1 98.0 100.0 100.9 100.3
101.1 99.5 98.4 98.9 105.3 102.6
101.7 99.6 102.5 98.3 99.5 101.0
99.9 101.8 102.0 100.6 100.2 102.3
98.6 99.6 99.7 97.6 100.5 97.5
mean 100.2 100.0 100.3 99.1 101.8 100.5

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was perfommed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -0.5% for samples that were resealed with new septa, and -3.7% for those that retained their punctured septa.

Table 4.10.2.1.2
Stability of Desorbed Samples for Enflurane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

99.5 99.4 -0.1 105.3 99.3 -6.0
100.2 98.9 -1.3 103.9 99.8 -4.1
100.5 100.3 -0.2 100.9 99.8 -1.1
(averages) (averages)
100.1 99.5 -0.5 103.4 99.6 -3.7

4.10.2.2 Halothane

The desorption efficiencies (DE) of halothane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the 5-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.3%.

Table 4.10.2.2.1
Desorption Efficiency of Halothane from Anasorb 747 at High TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 243.5 486.2 972.4 2431 4862 9724

DE (%) 98.9 98.9 100.0 99.9 99.3 99.1
98.7 98.2 98.1 -100.1 100.6 98.4
100.4 98.2 101.5 100.2 100.1 100.7
100.6 98.3 100.4 100.5 96.5 99.6
100.4 98.1 101.3 99.3 96.6 101.1
98.7 99.9 100.8 100.7 97.0 97.1
mean 99.6 98.6 100.4 100.1 98.4 99.3

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after infflal analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was +1.5% for samples that were resealed with new septa, and -1.6% for those that retained their punctured septa.

Table 4.10.2.2.2
Stability of Desorbed Samples for Halothane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

96.5 96.6 +0.1 99.3 98.0 -1.36
96.6 98.6 +2.0 100.6 99.0 -1.6
97.0 99.3 +2.3 100.1 98.3 -1.8
(averages) (averages)
96.7 98.2 +1.5 100.0 98.4 -1.6

4.10.2.3 Isoflurane

The desorption effciencies (DE) of isoflurane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the 75-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 100.2%.

Table 4.10.2.3.1
Desorption Efficiency of Isoflurane from Anasorb 747 at High TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 336 672 1344 3360 6720 13440

DE (%) 97.9 97.7 99.3 100.3 102.8 98.3
98.5 96.6 96.4 101.5 104.0 99.5
99.3 97.1 100.2 98.2 99.6 101.7
98.9 96.7 99.9 100.4 100.1 100.2
96.9 98.6 101.3 100.3 99.5 101.3
96.7 96.6 97.1 99.6 99.1 96.5
mean 98.0 97.2 99.0 100.1 100.9 99.6

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -3.4% for samples that were resealed with new septa, and -4.8% for those that retained their punctured septa.

Table 4.10.2.3.2
Stability of Desorbed Samples for Isoflurane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

100.1 94.0 -6.1 102.8 97.2 -5.6
99.5 96.4 -3.1 104.0 97.2 -6.8
99.1 98.1 -1.0 99.6 97.6 -2.0
(averages) (averages)
99.6 96.2 -3.4 102.1 97.3 -4.8

4.10.3 Anasorb CMS at low target concentration (TC)

4.10.3.1 Enflurane

The desorption efficiencies (DE) of enflurane were determined by liquid-spiking 150 mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 1-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 100.3%.

Table 4.10.3.1.1
Desorption Efficiency of Enflurane from Anasorb CMS at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.56 9.12 18.24 45.6 91.2 182.4

DE (%) 99.4 100.2 99.5 101.0 98.7 99.1
99.2 98.7 99.3 102.2 98.7 100.2
101.4 101.2 97.7 101.1 97.7 101.8
101.5 100.0 99.0 101.3 98.7 100.4
99.4 101.6 100.0 99.4 99.4 102.8
99.4 100.5 101.7 100.9 100.3 101.8
mean 100.2 100.4 99.5 101.0 98.9 101.0

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was perfommed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was +3.3% for samples that were resealed with new septa, and +0.9% for those that retained their punctured septa.

Table 4.10.3.1.2
Stability of Desorbed Samples for Enflurane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

98.7 101.4 +2.7 98.7 98.7 0
98.7 101.9 +3.2 99.4 99.8 +0.4
97.7 101.7 +4.0 100.3 102.8 +2.5
(averages) (averages)
98.4 101.7 +3.3 99.5 100.4 +0.9

4.10.3.2 Halothane

The desorption efficiencies (DE) of enflurane were determined by liquid-spiking 150-mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 1-ppm target concentration. These samples were stored overnight at ambient temperature and the desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.7%.

Table 4.10.3.2.1
Desorpbon Efficiency of Halothane from Anasorb CMS at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.862 9.724 19.45 48.62 97.24 194.5

DE (%) 101.1 100.3 100.8 99.1 98.7 98.2
99.7 103.2 99.1 98.3 99.5 98.7
98.8 99.5 100.8 100.3 99.1 100.1
99.7 100.0 98.5 100.0 100.2 100.5
99.5 100.5 99.4 98.9 102.4 100.1
98.9 99.7 100.2 97.5 101.1 101.7
mean 99.6 100.5 99.8 99.0 100.2 99.9

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 2.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were eanalyzed with fresh standards. The average percent change was +1.1% for samples that were resealed with new septa, and -1.6% for those that retained their punctured septa.

Table 4.10.3.2.2
Stability of Desorbed Samples for Halothane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

98.7 100.9 +2.2 100.2 99.3 -0.9
99.5 99.5 0 102.4 99.2 -3.2
99.1 100.1 +1.0 101.1 100.4 -0.7
(averages) (averages)
99.1 100.2 +1.1 101.2 99.6 -1.6

4.10.3.3 Isoflurane

The desorption efficiencies (DE) of isoflurane were determined by liquid-spiking 150-mg portions of Anasorb CMS with amounts equivalent to 0.05 to 2 times the 1-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.4%.

Table 4.10.3.3.1
Desorption Efficiency of Enflurane from Anasorb CMS at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.50 9.00 18.0 45.0 90.0 183.0

DE% 98.6 99.3 100.2 100.3 96.9 98.6
99.3 98.1 98.1 98.9 97.6 100.2
99.1 98.5 101.1 101.3 97.1 101.5
99.0 98.3 100.1 99.6 97.9 98.7
100.1 97.2 98.5 100.2 98.5 101.6
99.5 99.0 101.4 100.6 98.4 100.4
mean 99.3 98.4 99.9 100.2 97.7 100.2

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was perfomned, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was +3.6% for samples that were resealed with new septa, and +1.9% for those that retained their punctured septa.

Table 4.10.3.3.2
Stability of Desorbed Samples for Enflurane from Anasorb CMS

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

96.9 101.6 +4.7 97.9 97.1 -0.8
97.6 99.8 +2.2 98.5 101.1 +2.6
97.1 101.1 +4.0 98.4 102.5 +4.1
(averages) (averages)
97.2 100.8 +3.8 98.3 100.2 +1.9

4.10.4 Anasorb 747 at low target concentration (TC)

4.10.4.1 Enflurane

The desorption efficiencies (DE) of enflurane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the 1-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 103.7%.

Table 4.10.4.1.1
Desorption Efficiency of Enflurane from Anasorb 747 at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.56 9.12 18.24 45.6 91.2 182.4

DE (%) 102.0 100.5 99.1 103.2 102.3 101.9
102.2 100.2 98.4 102.3 104.2 105.3
96.9 97.9 99.6 102.2 101.6 103.7
102.4 98.2 98.2 100.9 104.6 103.8
101.2 97.7 99.7 107.8 106.3 103.6
102.9 99.4 99.0 107.4 100.6 104.6
mean 101.3 99.0 99.0 104.0 103.3 103.8

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -2.1% for samples that were resealed with new septa, and -2.9% for those that retained their punctured septa.

Table 4.10.4.1.2
Stability of Desorbed Samples for Enflurane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

102.3 98.4 -3.9 104.6 99.4 -5.2
104.2 100.9 -3.3 106.3 101.9 -4.4
101.6 102.6 +1.0 100.6 101.4 +0.8
(averages) (averages)
102.7 100.6 -2.1 103.8 100.9 -2.9

4.10.4.2 Halothane

The desorption efficiencies (DE) of halothane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the1-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 99.6%.

Table 4.10.4.2.1
Desorption Efficiency of Halothane from Anasorb 747 at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.862 9.724 19.45 48.62 97.24 194.5

DE(%) 85.2 95.7 94.8 98.0 98.3 101.0
84.5 93.3 97.2 98.3 100.2 100.9
85.2 92.7 94.3 99.7 97.9 99.0
83.1 91.7 94.2 99.8 100.9 98.9
84.5 90.7 93.7 99.7 101.6 99.1
83.5 91.4 94.2 98.9 100.7 100.5
mean 84.3 92.6 94.7 99.1 99.9 99.9

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was ±0% for samples that were resealed with new septa, and -3.0% for those that retained their punctured septa.

Table 4.10.4.2.2
Stability of Desorbed Samplies for Halothane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

98.3 98.4 +0.1 100.9 97.6 -3.3
100.2 98.1 -2.1 101.6 97.8 -3.8
97.9 99.9 +2.0 100.7 98.9 -1.8
(averages) (averages)
98.8 98.8 ±0 101.1 98.1 -3.0

4.10.4.3 Isoflurane

The desorption efficiencies (DE) of isoflurane were determined by liquid-spiking 140-mg portions of Anasorb 747 with amounts equivalent to 0.05 to 2 times the 1-ppm target concentration. These samples were stored overnight at ambient temperature and then desorbed and analyzed. The average desorption efficiency over the working range of 0.5 to 2 times the target concentration is 100.8%.

Table 4.10.4.3.1
Desorption Efficiency of Isoflurane from Anasorb 747 at Low TC

× target concn 0.05× 0.1× 0.2× 0.5× 1.0× 2.0×
(µg/sample) 4.50 9.00 18.0 45.0 90.0 180.0

DE (%) 97.1 100.0 98.1 103.2 99.3 99.4
92.3 99.6 102.2 97.6 99.9 102.8
96.4 100.2 101.1 99.4 99.2 100.8
97.8 100.0 102.5 98.5 101.5 101.7
99.4 100.0 101.0 104.0 102.9 100.8
97.9 100.1 101.4 103.8 97.5 101.5
mean 96.8 100.0 101.1 101.1 100.1 101.2

The stability of desorbed samples was investigated by reanalyzing the target concentration samples 22.5 h after initial analysis. After the original analysis was performed, three vials were recapped with new septa while the remaining three retained their punctured septa. The samples vials were stored in the refrigerated sampling tray for the GC injector. The samples were reanalyzed with fresh standards. The average percent change was -1.3% for samples that were resealed with new septa, and -4.4% for those that retained their punctured septa.

Table 4.10.4.3.2
Stability of Desorbed Samples for Isoflurane from Anasorb 747

punctured septa replaced punctured septa retained
initial DE after initial DE after
DE one day difference DE one day difference
(%) (%) (%) (%)

99.3 97.4 -1.9 101.5 96.8 -4.7
99.9 97.0 -2.9 102.9 95.0 -7.9
99.2 100.2 +1.0 97.5 96.8 -0.7
(averages) (averages)
99.5 98.2 -1.3 100.6 96.2 -4.4

4.11 Qualitative analysis

The anesthetic gases can be easily separated and identified by GCA\MS. Mass spectra for enflurane, halothane and isoflurane, which were separated using conditions similar to the information given in Section 3.5, were obtained from a Perkin-Elmer Ion Trap Detector interfaced to a Hewlett-Packard Series II GC.

graph

Figure 4.11.1. Mass spectrum of enflurane.


graph

Figure 4.11.2. Mass spectrum of halothane.


graph

Figure 4.11.3. Mass spectrum of isoflurane.

4.12 Nitrous oxide interference

A test was developed to study the ability of nitrous oxide to interfere with the collection of anesthetic gases on the recommended sampling tubes. A 100-L gas-sampling bag was filled with dry air and 1.50 mL of water was added to raise the humidity to 80% at 22°. Halothane was selected as a typical anesthetic gas and 20µL (37.4 mg) was added to the bag. Nitrous oxide (430.5 mg) was also added. This produced an atmosphere containing 46.4 ppm of halothane and 2390 ppm of nitrous oxide. A second bag was prepared to dupiclate the first one except no nitrous oxide was added. Air samples were drawn at 0.05 L/min for 4 h from both bags using Anasorb CMS and Anasorb 747. No halothane was detected on any of the back-up sections. The results show that nitrous oxide does not substantially interfere with the collection of halothane from an atmosphere containing both gases.

Table 4.12
Parts-per-million recovered from Gas-Sampling Bags

Anasorb halothane halothane with
nitrous oxide

CMS 44.9 40.3
747 45.6 45.7

5. References

5.1 OSHA Analytical Methods Manual, 2nd ed., U.S. Department of Labor, Occupational Safety and Health Administration; Salt Lake Technical Center; Salt Lake City, UT 1993; "Method 29 - Enflurane and Halothane" (1981); American Conference of Governmental Industrial Hygienists (ACGIH); Cincinnati, OH, Publ. No. 4542.

5.2 NIOSH Criteria for a Recommended Standard: Occupational Exposure to Waste Anesthetic Gases and Vapors, U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Health for Occupational Safety and Health, Cincinnati, OH, 1977, DHHS (NIOSH) Publ. 77-140.

5.3 NIOSH Recommendations for Occupational Safety and Health: Compendium of Policy Documents and Statements, U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Health for Occupational Safety and Health, Cincinnati, OH, 1992, DHHS (NIOSH) Publ. 92-100.

5.4 Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed., American Conference of Governmental Industrial Hygienists (ACGIH); Cincinnati, OH, 1986.

5.5 MRC Monograph on the Evaluation of Carcinogenic Risks to Humans: Overall Evaluation of Carcinogenicity: An Update of IARC Monographs Volumes 1 to 42, International Agency for Research on Cancer (IARC), Lyon, France, 1987, Supplement 7, pp. 93-95.

5.6 Material Safety Data Sheet: Ethrane, Anaquest, Liberty Corner, NJ, March 1992.

5.7 Material Safety Data Sheet: Forane, Anaquest, Liberty Corner, NJ, March 1992.

5.8 Material Safety Data Sheet 2-Bromo-2-chloro-1,1,1-trifluoroethane, Aldrich Chemical Co., Milwaukee, WI, May 1992.

5.9 Merck Index, Budavari, S. Ed., 11th ed., Merck & Co., Rahway, NJ, 1989.

5.10 OSHA Instruction CPL 2-2.60, Exposure Control Plan for Federal OSHA Personnel with Occupational Exposure to Bloodbome Pathogens, March 7,1994; Occupational Safety and Heath Administration, U.S. Department of Labor, Washington, D.C.