Determination of Ethylene Glycol and Diethylene Glycol by GC-FID

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1.0 Purpose 
 
 1.1 The purpose of this SOP is to define the method for the determination of ethylene
 glycol and diethylene glycol in raw materials and finished products by GC-FID.
 
 2.0 Scope 
 
 2.1 This procedure applies to the determination of ethylene glycol and diethylene glycol in
 raw materials and finished products in the QC Laboratory at Ion Labs.
 
 Due This procedure does not apply to the limit of ethylene glycol and diethylene glycol in
 glycerin, propylene glycol, and sorbitol raw materials. 
 
 3.0 Responsibility 
 3.1 It is the responsibility of QC Chemists to follow this procedure. 
 
 3.2 It is the responsibility of QC Laboratory Management to ensure that this procedure is
 being followed. 
 
 3.3 It is the responsibility of QC Laboratory Management/Analytical Development to keep
 SOP aligned with current practices. 
 
 4.0 Definitions 
 
 4.1 QC Quality control 
 4.2 GC-FID Gas chromatography with flame ionization detection 
 
 4.3 CoA Certificate of analysis 
 
 44 EG Ethylene glycol 
 4.5 DEG Diethylene glycol 
 
 4.6 TCE 2,2,2-trichloroethanol 
 
 4.7 PTFE _ Polytetrafluoroethylene 
 5.0 References 
 
 5.1 PRTCL-21-0021: Validation of an Analytical Method for the Determination of
 Ethylene Glycol and Diethylene Glycol by GC-FID 
 
 
 

[SOP D-100 | Page 2 of 5]

 Standard Operating Procedure 
 Determination of Ethylene Glycol and Diethylene Glycol apie 7 bi 
 by GC-FID : of 5 
 
 a PRTCL-20-0015: Verification of an Analytical Method for the Limit of Diethylene
 Glycol and Ethylene Glycol in Glycerin and Propylene Glycol Raw Materials
 
 6.0 Supplies 
 
 6.1 Chemicals (all chemicals ACS reagent grade or better) 
 
 6.1.1 Ethylene Glycol Reference Standard 
 6.1.2 Diethylene Glycol Reference Standard 
 
 6.1.3 TCE 
 
 6.1.4 Methanol 
 6.2 Compressed Gases (use ultra-high purity gases) 
 
 6.2.1 Hydrogen 
 
 6.2.2 Helium 
 6.2.3 Air 
 
 6.2.4 Nitrogen 
 
 6.3 Supplies and Glassware 
 
 6.3.1 Volumetric glassware as required for standard and sample preparation
 6.3.2 2-mL GC vials with PTFE lined closures 
 
 6.3.3. 2-mL Eppendorf centrifuge tubes 
 
 6.3.4 Pipet Tips 
 6.4 Equipment 
 
 6.4.1 Agilent 7890 GC with FID detector 
 
 6.4.2 Analytical Balance 
 6.4.3. Adjustable Pipet 
 
 6.4.4 Centrifuge 
 
 7.0 GC Conditions 
 
 7.1 Column: Rxi-624SiIMS, 30 m x 0.32 mm x 1.8 um or equivalent 
 Vee Inlet Liner: Restek, 4.0 mm ID x 6.3 mm OD x 78.5 mm length straight liner
 with glass wool or equivalent 
 
 7.3 Inj Temp: 220 °C 
 
 7.4 Det Temp: 250°C 
 7.5 Equil Time: 0.5 min 
 
 
 

[SOP D-100 | Page 3 of 5]

 Standard Operating Procedure 
 SOP No Rev Page | 
 Determination of Ethylene Glycol and Diethylene Glycol 
 D-1002 0 3 of 5 
 by GC-FID 
 7.6 FlowRate: 2.5 mL/min 
 7.7 RunTime: 22.4 min 
 
 7.8 Split ratio: 10:1 
 7.9 Septum purge: 3 mL/min 
 
 7.10 Air flow: 350 mL/min 
 
 7.11 Fuel flow: 30 mL/min 
 7.12 Makeup flow: 30 mL/min (column + makeup = constant) 
 
 7.13 Injection Volume 1 wh 
 
 7.14 Injection Type Standard 
 7.15 Plunger Speed Fast 
 
 7.16 Wash Solvent Methanol 
 
 7.17 Temperature Ramp: 
 
 Ramp Rate Hold Time 
 (°C/min) T SOD ALe)e lenin) 
 
 N/A 100 4A 
 
 50 120 10 
 
 50 220 6 
 
 8.0 Diluent 
 
 8.1 Transfer 65 uL of TCE to a 1-L media bottle. 
 8.2 Add 1000 mL of methanol 
 
 8.3. Mix well. 
 
 9.0 Stock Standard Preparation 
 
 9.1 Transfer 200 + 2 mg of EG reference standard to a small beaker or vial.
 sae Transfer 200 + 2 mg of DEG reference standard to a small beaker or vial.
 
 9.3. Use small portions of Diluent to quantitatively transfer the EG and DEG into a 50-mL
 volumetric flask. 
 
 9.4 Dilute to volume with Diluent and mix well. 
 
 
 

[SOP D-100 | Page 4 of 5]

 Standard Operating Procedure 
 Determination of Ethylene Glycol and Diethylene Glycol papith ay ree 
 by GC-FID : ‘ 
 
 10.0 Working Standard Preparation 
 
 10.1 Transfer 0.625 mL of Stock Standard to a 50-mL volumetric flask. 
 
 10.2. Dilute to volume with Diluent and mix well. 
 11.0 Sample Preparation 
 
 bit The validated linear range of the method is 2 — 200 mcg/mL. The sample preparation
 
 must be within the linear range. 
 11.2 To manage large volumes, the sample can be initially dissolved in a smaller volume that
 is within the solubility range and a portion further diluted to bring the analyte
 
 concentration into the linear range of measurement. 
 11.3 For finished products, pool at least 10 dosage units and homogenize. Based on the
 
 dosage weight (for powders), fill weight (for capsules) or tablet weight and the limit
 level, weigh no less than 20 mg of the pooled dosages into a suitably sized volumetric
 flask to generate a concentration within the validated linear range, add Diluent to about
 2/3 of the flask volume and shake for at least 20 minutes. Dilute to volume with
 Diluent, and sonicate for 5 minutes. 
 
 11.4 For raw materials, based on the limit level, weigh no less than 20 mg of sample into a
 suitably sized volumetric flask to generate a concentration within the linear range, add
 
 Diluent to about 2/3 of the flask volume and shake for at least 20 minutes. Dilute to
 volume with Diluent, and sonicate for 5 minutes. 
 11.5 If particulates remain in sample preparations, filter through a 0.45 um membrane,
 
 discarding a portion before collecting the sample for analysis. Alternatively, centrifuge
 to remove particulates. 
 
 12.0 Recommended Sequence 
 12.1 Make two injections of Diluent 
 
 12.2 Make five injections of Working Standard 
 
 12.3 Make a single injection of each Sample Preparation 
 
 13.0 System Suitability Requirements 
 13.1 No significant (>0.5%) interfering peaks are present in the blank injection.
 
 13.2 The %RSD of the peak area ratio in five consecutive injections of the Working
 Standard is NMT 10.0%. 
 
 14.0 Retention Times 
 
 14.1 EG 3.4 min 
 14.2 TCE 6.8 min 
 
 
 

[SOP D-100 | Page 5 of 5]

 eieescameiarenaacpotest pe oe Glycol pogd— ay vi Spe 
 
 by GC-FID 
 
 14.3. DEG 9.4 min 
 
 13.0 Example Calculations 
 
 Ry. Weg PV. 
 Assay (%) = = x a x an x 100 
 
 Re Sample peak area ratio 
 R. Mean Working Standard A peak area ratio (5 injections) 
 
 Wtstqa Weight of reference standard used to prepare Working Standard (mg)
 
 P Purity of reference standard from the CoA (% w/w) 
 
 V sta Volume of Working Standard (mL) 
 Vn Volume of Sample Solution (mL) 
 
 Splwt Sample weight (mg) 
 
 16.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 05/29/20 | New N/A S. Sassman | - | - |