D-754

Residual Solvents by Headspace GC

Section D — Laboratory Operations and Specifications Revision 2 17 pages

Original Document

Scanned document (image-only PDF)

Extracted Text

Searchable text extracted from PDF

1.0 Purpose

This procedure describes a method for the identification and quantification of residual solvents.

2.0 Scope

This procedure applies to the identification and quantification of residual solvents in dietary

supplements, dietary ingredients, pharmaceuticals, and cosmetics in the QC laboratory.

3.0 Responsibility

Sal It is the responsibility of QC and Analytical Chemists to follow this procedure.

3.2 It is the responsibility of QC Laboratory Management to implement this procedure and

to ensure that the procedure is being followed.

3.3. It is the responsibility of QC Laboratory Management and/or Analytical Development

personnel to keep this procedure aligned with current practices.

4.0 Definitions

4.1 GC — Gas Chromatography

4.2. DMSO —- Dimethyl sulfoxide

4.3. QC - Quality Control

4.4 CofA -— Certificate of Analysis

4.5 USP — United States Pharmacopeia

4.6 RS- Reference Standard

5.0 References

5,1 USP General Chapter <467> Residual Solvents

[SOP

Standard Operating Procedure SOP No Rev
Residual Solvents by Headspace GC D-754 Page 2 of 17

5.2 USP General Chapter <1467> Residual Solvents

5.3. D-725, SOP, Loss on Drying

54 MV-LAB-19-178, Protocol, Validation of a Method for the Limit of Isopropyl Alcohol
in Oil

6.0 Reagents, Supplies, Glassware and Equipment

6.1 Reagents: all reagents are GC grade or better.

6.1.1 Millipore deionized water

6.1.2 DMSO

6.1.3 Residual solvent reference standards

6.1.4 Compressed hydrogen, helium, air, and nitrogen

6.2 Supplies and Glassware

6.2.1 Headspace GC vials, with crimp cap enclosures w/ septa

6.2.2 10-mL and 100-mL volumetric flasks

6.2.3 50-mL and 100-mL beakers

6.2.4 200-uL, 1-mL, and 10-mL pipette tips

6.2.5 Weigh boats

6.3. Equipment

6.3.1 Agilent 7697A Headspace Analyzer

6.3.2 Agilent 7890B GC System

6.3.3 Analytical Balance

6.3.4 Vortex

6.3.5 200-uL, 1-mL and 10-mL pipettes

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page3of17

7.0 Procedure Outline

7.1 Procedure A is a limit test used to identify Class 1 and Class 2 residual solvents that
may be present.

7.2 Procedure B utilizes chromatographic separation with different selectivity to confirm

any residual solvent previously identified by Procedure A. Confirmation by Procedure

B is optional; the analyst may choose to proceed directly to Procedure C.

te For residual solvents that have been identified as present by Procedure A/B or identified
as likely to be present by the raw material manufacturer, quantitation is necessary. Use

Procedure C to quantitate the residual solvents that are present.

7.4 If only specific solvents need to be quantified, Procedure C may be used directly.

7.5 Procedure D (Loss on Drying) may be used to evaluate the limit of Class 3 residual

solvents if they are likely to be present. If the LOD is greater than 0.5% (5000 ppm) or
the sample is not amenable to LOD (e.g. an aqueous solution) then it is necessary to

quantitate the Class 3 solvents that are likely to be present by Procedure C.

7.6 An outline of the procedure for identification and quantitation of Class 1 and 2 residual
solvents is shown in Figure 1.

[SOP

Standard Operating Procedure SOP No Rev
Residual Solvents by Headspace GC D-754 Page 4 of 17

Preparation of test
and standard solutions
v
| Procedure A |

Peak areas in
Passes the test
sample are smaller
No further action
than standard?
Procedure B

Peak areas in
Passes the test
sample are smaller
No further action
than standard?
No
procedure C |
Label to indicate
v
residual solvent
Calculate amount of and amount found
residual solvent(s) found
v
is the Meets
article under test concentration
an official limits for residual
product? solvents?
Meets
concentration Yes Passes the test
limits for residual No further action
solvents?
| Fails the test |
Figure 1: Outline of Procedure for Identification and Quantitation of Residual Solvents
8.0 Limits

8.1 The limits given for each residual solvent in USP <467> are listed in Table 1.

8.2 USP <467> places the each residual solvent in a class based on toxicity:

8.2.1 Class 1 — suspected or known human carcinogens

8.2.2 Class 2 —high toxicity

[SOP

Standard Operating Procedure SOP No Rev
Residual Solvents by Headspace GC D-754 2 Page 5 of 17

8.2.3. Class 3 — low toxicity (no health based exposure limit)

Table 1: Limits for Residual Solvents

Solvent Class | Mixture PDE (mg/day) Conc Limit (ppm)
Benzene l N/A N/A 2
Carbon tetrachloride l N/A N/A 4
1,2-Dichloroethane l N/A N/A 5
1,1-Dichloroethene i N/A N/A 8
1,1,1-Trichloroethane 1 N/A N/A 1500
Acetonitrile 2 A 4.1 410
Chlorobenzene 2 A 3.6 360

Chloroform 2 B 0.6 60
Cumene 2 A 0.7 70
Cyclohexane 2 A 38.8 3880
1,2-Dichloroethene 2 A 18.7 1870
1,2-Dimethoxyethane 2 B l 100
N,N-Dimethylacetamide 2 C 10.9 1090
N,N-Dimethylformamide 2 C 8.8 880
1,4-Dioxane 2 A 3.8 380
2-Ethoxyethanol 2 C 1.6 160
Ethylene glycol 2 & 6.2 620

Formamide 2 C 2.2 220
Hexane 2 B 2.9 290
Methanol pi A 30 3000
2-Methoxyethanol pi C 0.5 50
Methylbutylketone 2 B 0.5 50
Methylcyclohexane 2 A 11.8 1180
Methylene chloride 2 A 6 600
N-Methylpyrrolidone 2 C 5.3 530
Nitromethane 2 B 0.5 50
Pyridine 2 B 2 200
Sulfolane 2 C 1.6 160

Tetrahydrofuran 2 A 7.2 720
Tetralin Z B Il 100
Toluene 2 A 8.9 890
Trichloroethylene 2 B 0.8 80
Xylene ! 2 A 21.7 2170
Class 3 Residual Solvents 3 N/A 50 5000
| Usually 60% m-xylene, 14% p-xylene, 9% o-xylene with 17% ethyl benzene.

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 6 of 17

9.0 Procedure A (Identification)

9.1 Preparation

9.1.1 Water Soluble Articles

9.1.1.1 Blank Solution - Transfer 6.0 mL of water to a 10-mL headspace vial,

apply stopper, crimp cap and mix.

ee Sample Stock Solution — 10 or more dosage units can be pooled and
ground by mortar and pestle as necessary. Weigh and transfer about

250 mg of sample to a 25-mL volumetric flask, dissolve and dilute
with water to volume and mix.

9.1.1.3 Sample Solution — Transfer 5.0 mL of Sample Stock Solution to a 10-

mL headspace vial, add 1.0 mL of water, apply stopper, crimp cap and

mix.

9.1.1.4 Class 1 Standard Stock Solution - Add 1.0 mL USP Class 1 residual
solvents mixture RS to a 100-mL volumetric flask previously filled

with 9 mL DMSO, and dilute with water to volume. Transfer 1.0 mL
of the resulting solution to a 100-mL volumetric flask filled about

halfway with water. Dilute to volume with water and mix. Transfer 10

mL of this solution to a 100-mL volumetric flask filled about halfway
with water. Dilute to volume and mix.

9.1.1.5 Class 1 Standard Solution - Transfer 1.0 mL of Class 1 Standard Stock

Solution to a 10-mL headspace vial containing 5 mL water, apply
stopper, crimp cap and mix.

9.1.1.6 Class 2 Mixture A Standard Stock Solution - Add 1.0 mL USP
Residual Class 2 — Mixture A RS to a 100-mL volumetric flask filled

about halfway with water. Dilute to volume with water then mix.

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 7 of 17

tee ee Class 2 Mixture A Standard Solution- Transfer 1.0 mL of Class 2

Mixture A Standard Stock Solution to a 10-mL headspace vial

containing 5 mL of water, apply stopper, crimp cap and mix.

9.1.1.8 Class 2 Mixture B Standard Stock Solution - Add 1.0 mL USP
Residual Class 2 — Mixture B RS to a 100-mL volumetric flask filled

about halfway with water. Dilute to volume with water then mix.

9.1.1.9 Class 2 Mixture B Standard Solution - Transfer 1.0 mL of Class 2

Mixture B Standard Stock Solution to an 10-mL headspace vial
containing 5 mL of water, apply stopper, crimp cap and mix.

9.1.1.10 System Suitability Solution- Transfer 1.0 mL of Class 1 Standard

Stock Solution to a 10-mL headspace vial, add 5.0 mL of Sample
Stock Solution, apply stopper, crimp cap and mix.

9.1.2 Water Insoluble Articles

ee| Blank Solution - Transfer 1.0 mL of DMSO and 5.0 mL of water to a
10-mL headspace vial, apply stopper, crimp cap and mix.

9.1.2.2 Sample Stock Solution — 10 or more dosage units can be pooled and

ground by mortar and pestle as necessary. Weigh and transfer about
500 mg of sample to a 10-mL volumetric flask, dissolve and dilute

with water to volume and mix.

9.1.2.3 Sample Solution — Transfer 1.0 mL of Sample Stock Solution to a 10-
mL headspace vial, add 5.0 mL of water, apply stopper, crimp cap and

mix.

9.1.2.4 Class 1 Standard Stock Solution - Add 1.0 mL USP Class 1 residual

solvents mixture RS to a 100-mL volumetric flask previously filled
with about 80 mL DMSO, dilute with DMSO to volume and mix.

Transfer 1.0 mL of the resulting solution to a 100-mL volumetric flask
containing about 80 mL of DMSO, dilute to volume and mix (reserve a

portion of this solution for the Class 1 System Suitability Solution).

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 8 of 17

Transfer 1.0 mL of this solution to a 10-mL volumetric flask, dilute to
volume with DMSO and mix.

9.1.2.5 Class 1 Standard Solution - Transfer 1.0 mL of Class 1 standard stock

solution to a 10-mL headspace vial containing 5 mL water, apply
stopper, crimp cap and mix.

9.1.2.6 Class 2 Mixture A Standard Stock Solution — Add 1.0 mL USP
Residual Class 2 — Mixture A RS to a 100-mL volumetric flask

containing about 80 mL of DMSO, dilute to volume with DMSO and
mix.

9.1.2.7 Class 2 Mixture A Standard Solution- Transfer 1.0 mL of Class 2

Mixture A Standard Stock Solution to a 10-mL headspace vial

containing 5 mL of water, apply stopper, crimp cap and mix.

9.1.2.8 Class 2 Mixture B Standard Stock Solution - Transfer 0.5 mL USP
Residual Class 2 — Mixture B RS to a 10-mL volumetric flask

containing about 5 mL of DMSO, dilute to volume with DMSO and
mix.

9.1.2.9 Class 2 Mixture B Standard Solution - Transfer 1.0 mL of Class 2

Mixture B Standard Stock Solution B to a 10-mL headspace vial

containing 5 mL of water, apply stopper, crimp cap and mix.

9.1.2.10 System Suitability Solution- Mix 5.0 mL of Sample Stock Solution
with 0.5 mL of the intermediate dilution reserved from Class 1

Standard Stock Solution. Transfer 1.0 mL of the resulting solution to a
10-mL headspace vial containing 5.0 mL of water, apply stopper,

crimp cap and mix.

9.2 Analysis

9.2.1 Using the chromatographic conditions outlined in Section 12.1, separately inject

equal volumes of headspace of the System Suitability Solution, Class 1 Standard
Solution, Class 2 Mixture A Standard Solution, Class 2 Mixture B Standard

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page9 of 17

Solution, Blank Solution, and Sample Solution into the GC system and measure

the responses for the peaks-of-interest.

9.3. System Suitability Requirements

9.3.1 The signal-to-noise (S/N) ratio for 1,1,1-trichloroethane in the Class 1 Standard

Solution is NLT 5.

9.3.2 The S/N ratio of each peak in the System Suitability Solution is NLT 3.

9.3.3 The resolution between acetonitrile and methylene chloride in the Class 2

Mixture A Standard Solution is NLT 1.0.

9.4 Acceptance Criteria

9.4.1 Ifthe peak response for any peak other than 1,1,1-trichloroethane in the sample
solution is > a corresponding peak in any of the standard solutions or 1,1,1-

trichloroethane is > 150 times the peak response in the Class 1 standard solution,
proceed to Section 10.0 (Procedure B) to confirm the peak.

9.4.2 If no peak response for any peak is > to the peaks in the standard solutions

and/or the peak for 1,1,1-trichloroethane is < 150 times the peak from the

standard solutions then the sample passes without any need for further tests.

9.5 Method Verification

9.5.1 No additional work is necessary for verification of Procedure A. The System
Suitability acceptance criteria satisfy all of the method verification requirements

outlined in USP <1467>.

10.0 Procedure B (Confirmation)

10.1. Preparation and Analysis

10.1.1 Use the same Standards and Samples prepared in Procedure A (Section 9.1).

10.2 Analysis

10.2.1 Using the chromatographic conditions outlined in Section 12.2, separately inject

equal volumes of headspace of the System Suitability Solution, Class 1 Standard

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 10 of 17

Solution, Class 2 Mixture A Standard Solution, Class 2 Mixture B Standard

Solution, Blank Solution, and Sample Solution into the GC system and measure

the responses for the peaks-of-interest.

10.3. System Suitability Requirements

10.3.1 The S/N ratio for benzene in the Class 1 Standard Solution is NLT 5.

10.3.2 The S/N ratio for each peak in the System Suitability Solution is NLT 3.

10.3.3 The resolution between acetonitrile and cis-dichloroethene in the Class 2

Mixture A Standard Solution is NLT 1.0.

10.4 Acceptance Criteria

10.4.1 If the peak response for any peak in the sample solution is = a corresponding
peak in any of the standard solutions, proceed to Section 11.0 (Procedure C) to

quantify the peak.

10.4.2 If no peak response for any peak is > to the peaks in the standard solutions, then
the sample passes without any need for further tests.

10.5 Method Verification
10.5.1 No additional work is necessary for verification of Procedure B. The System

Suitability acceptance criteria satisfy all of the method verification requirements

outlined in USP <1467>.

11.0 Procedure C (Quantitation)

11.1 Preparation

11.1.1 Water Soluble Articles

11.1.1.1 Blank Solution — Transfer 6.0 mL of water to a 10-mL headspace vial,

apply stopper, crimp cap and mix.

11.1.1.2 Standard Stock Solutions — (Note: Only solvents identified as present
by Procedure A or identified as likely to be present should be

quantified using Procedure C). For each residual solvent transfer an

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 11 of 17

accurately measured volume of the individual RS to a volumetric flask
filled about halfway with water, and dilute quantitatively and stepwise,

if necessary, with water to obtain a solution having a final
concentration of 1/20 the value stated in Table |. For Class 1 residual

solvents, the first dilution should be 1 mL to 100 mL.

11.1.1.3 Standard Solution — Transfer 1.0 mL of each Standard Stock Solution

to a 10-mL headspace vial containing 5.0 mL water, apply stopper,
crimp cap and mix.

11.1.1.4 Sample Solutions — Same as directed in Section 9.1.1 (Procedure A -

Water Soluble Articles).

11.1.1.5 Spiked Sample Solution — For each identified peak, transfer 5.0 mL of
Sample Stock Solution to a 10-mL headspace vial and add 1.0 mL of

the Standard stock solution, apply stopper, crimp cap and mix.

11.1.2 Water Insoluble Articles

11.1.2.1 Blank Solution — Transfer 1.0 mL of DMSO and 5.0 mL of water to a

10-mL headspace vial, apply stopper, crimp cap and mix.

11.1.2.2 Standard Stock Solutions — (Note: Only solvents identified as present
by Procedures A and/or B or identified as likely to be present should

be quantified using Procedure C). For each residual solvent transfer an

accurately measured volume of the individual RS to a volumetric flask,
and dilute quantitatively and stepwise, if necessary, with water to

obtain a solution having a final concentration of 1/20 the value stated
in Table 1. For Class 1 residual solvents, the first dilution should be 1

mL to 100 mL.

11.1.2.3 Standard Solution — Transfer 1.0 mL of each Standard Stock Solution
to a 10-mL headspace vial and add 5.0 mL water, apply stopper, crimp

cap and mix.

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 12 of 17

11.1.2.4 Sample Solutions — Same as directed for Section 11.1.2 (Procedure A -
Water Insoluble Articles).

11.1.2.5 Spiked Sample Solution —For each identified peak, transfer 1.0 mL of

each Sample Stock Solution to a 10-mL headspace vial, add 1.0 mL of
the Standard stock solution and 4.0 mL of water, apply stopper, crimp

cap and mix.

11.2 Analysis

11.2.1 Using the chromatographic conditions (Procedure A or Procedure B) that

resulted in the best separation for the solvents being quantitated, separately
inject equal volumes of headspace for the Blank Solution, Sample Solution,

Spiked Sample Solution(s), and Standard Solution(s) into the system and

measure the responses for the major peaks.

11.2.2 For each residual solvent, calculate the concentration in ppm of each residual
solvent found by the formula:

C un
Result esu = AX W— x r

Where A is a constant (A=5 for Water Soluble and A=10 for Water Insoluble

articles), C is the concentration of the Standard Stock Solution (ug/mL), W is

the weight of sample used to prepare the Sample Stock Solution (g), ru is the
peak response from the Sample Solution, and rs is the peak response from the

Spiked Sample Solution.

11.3. System Suitability Requirements

11.3.1 For each peak identified by Procedure A or deemed likely to be present, the S/N

ratio is NLT 10 for any solvent except NLT 5 for 1,1,1-trichloroethane or
benzene and NLT 3 for any other Class 1 solvent.

11.3.2 The resolution between any peak-of-interest and any adjacent peak is NLT 1.0.

11.4 Acceptance Requirements

[SOP

Standard Operating Procedure SOP No Rev
Residual Solvents by Headspace GC D-754 Page 13 of 17

11.4.1 If solvent being tested is less than the limit shown in Table 1, the sample passes

for that residual solvent.

11.5 Method Verification

11.5.1 If this is the first time that the article has been tested using Procedure C,

verification of the method is required. Refer to Section 13.0 for verification

requirements.

12.0 Chromatographic Conditions

12.1 Procedure A

12.1.1 Gas Chromatography Conditions

Column: ZB-624, 30 m x 0.32 mm x 1.8 um or equivalent

Oven Temp: 40°C

Temp. Gradient: 40°C hold for 20 min,

Ramp at 10°C/min to 240°C, and hold for 20 min

Pressure Gradient: 10 psi hold for 20 min,

Ramp at 0.21 psi/min to 14.2 psi, and hold for 20 min

Run Time: 60 min

Equil Time: 2 min

Inlet Temp: 140°C

Split Ratio: 5:1

Septum Purge: 2 mL/min

FID Temp: 250°C

Hydrogen: 30 mL/min

Air: 350 mL/min

Helium: 30 mL/min (constant column + makeup)

[SOP

Standard Operating Procedure SOP No Rev
Residual Solvents by Headspace GC D-754 Page 14 of 17

12.1.2 Headspace Conditions

Oven Temp: 80°C

Loop Temp: os

Transfer Line: L10*¢

Equil Time: 50 min

Injection Time: 0.5 min

GC Cycle Time: 67 min

Vial Size: 10 mL

Vial Fill Mode: Default: Flow to Pressure

Fill Pressure: 12 psi

Loop Fill Mode: Default

Extraction Mode: Single Extraction

Post Injection purge: Custom

Purge Flow: 100 mL/min

Purge Time: 2.5 min

12.2 Procedure B

12.2.1 Gas Chromatography Conditions

Column: ZB-WAXplus, 30 m x 0.32 mm x 0.25 um or equivalent

Oven Temp: SO°PC

Temp. Gradient: 50°C hold for 20 min,

Ramp at 6°C/min to 165°C, and hold for 20 min

Pressure Gradient: 10 psi hold for 20 min,

Ramp at 0.12 psi/min to 12.4 psi, and hold for 20 min

Run Time: 60 min

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC Dba | 2 | Kapeds old?

Equil Time: 2 min

Inlet Temp: 240°C

Split Ratio: 5:1

Septum Purge: 2 mL/min

FID Temp: 250°C

Hydrogen: 30 mL/min

Air: 350 mL/min

Helium: 30 mL/min (constant column + makeup)

12.2.2 Headspace Conditions

12.2.2.1 Headspace Conditions are the same as for Procedure A.

13.0 Procedure D (Loss on Drying)

13.1 Record all data and results on Form D-725-F1 Vacuum Oven LOD Test Record.

13.2 Equilibrate a vacuum oven to 105°C.

13.3. Dry aclean weigh bottle just before adding sample.

13.4 Record the weight of the clean and dry weigh bottle (tare weight).

13.5 Add 2.5 + 0.2 g of the sample to the tared container, and record the sample weight.

13.6 Place the open weigh bottle and lid into the vacuum oven.

13.7 Apply 20 + 4 inches of vacuum and leave in the oven under vacuum for 2 hours (solids)
or 3 hours (oils).

13.8 After the allotted time, remove the sample from the oven, replace the cap, and move the

sample to a desiccator to cool for 20 minutes. Use caution when moving samples as

they may be hot.
13.9 After cooling, record the weight of the weigh bottle and sample (final weight).

13.10 The % LOD is determined by the following equation:

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 16 of 17

(Tare Wt + Sample Wt) — Final Wt
%e o LOD = Sample Wt x 100

14.0 Method Verification

14.1. Method verification is only required for Procedure C. Verification involves preparing

samples spiked in triplicate at 50%, 100%, and 150% of the limit amount, and

measuring recovery of the spiked analyte.

14.2 Preparation of Spiked Sample Solutions

14.2.1 50% spike: Transfer 1.0 mL of Sample Stock Solution to a 10-mL headspace
vial, add 0.5 mL of the Standard Stock Solution and 4.5 mL of water, apply

stopper, crimp cap and mix.

14.2.2 100% spike: Transfer 1.0 mL of Sample Stock Solution to a 10-mL headspace
vial, add 1.0 mL of the Standard Stock Solution and 4.0 mL of water, apply

stopper, crimp cap and mix.

14.2.3 150% spike: Transfer 1.0 mL of Sample Stock Solution to a 10-mL headspace

vial, add 1.5 mL of the Standard Stock Solution and 3.5 mL of water, apply
stopper, crimp cap and mix.

14.3. Analysis

14.3.1 Using the chromatographic conditions (Procedure A or Procedure B) that

resulted in the best separation for the solvents being quantitated, separately
inject equal volumes of headspace for the Blank Solution, Sample Solution,

Spiked Sample Solution(s), and Standard Solution(s) into the system and
measure the responses for the major peaks.

14.3.2 For each residual solvent, calculate the recovery in % of each spiked residual

solvent.

14.4 Acceptance Criteria

14.4.1 Accuracy — The mean recovery for the nine spiked samples is 80% - 120%.

[SOP

Standard Operating Procedure SOP No | Rev
Residual Solvents by Headspace GC D-754 2 | Page 17 of 17

14.4.2 Precision — The %RSD of the recovery for the nine spiked sample is NMT 20%.

14.5 After verification has been performed, a report should be prepared and stored in the

F:\Laboratory\Residual Solvents\ folder.

15.0 Revision History

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 06/06/18 | New procedure N/A J. Maignan Update procedure to comply with the new general chapter USP | - | - |
| 1 | 11/26/19 | <1467>. Edit procedure for better flow and brevity. Add Procedure D for determination of Class 3 residual solvents by LOD. | 19-0894 | S. Sassman |
| 2 | 01/20/23 | Schedule review: updated logo and document format. CC- | 23-0036 | K. Burris |