D-768

Methylsulfonylmethane Determination by GC using FLame Ionization Detection

Section D — Laboratory Operations and Specifications Revision 2 9 pages

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1.0 Purpose 
 
 The purpose of this procedure is to define the method for the quantitation and/or identification
 of Methylsulfonylmethane in raw material and finished product dietary supplements by GC
 
 using flame ionization mode. 
 
 2.0 Scope 
 
 This procedure applies to the quantification and identification of MSM in raw materials and
 
 finished products. MSM readily detectable by FID on the GC using the direct inject mode.
 
 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 implement this procedure and
 to ensure that this procedure is being followed. 
 
 3.3 ‘It is the responsibility of QC Laboratory Management and/or Analytical Development
 to keep this procedure aligned with current practices. 
 
 4.0 Definitions 
 
 4.1 FID — Flame Ionization Detection 
 
 4.2 DGME — Di(ethylene glycol) methyl ether 
 
 4.3. MSM —-Methylsulfonylmethane or dimethyl sulfone 
 
 4.4 MeOH — Methanol 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Page 
 Methylsulfonylmethane Determination by GC using D-768 2 
 2 of 9 
 Flame Ionization Detection 
 5.0 References 
 
 5.1 USP 41 Methylsulfonylmethane Monograph 
 
 5.2. MV-LAB-18-069, Protocol, Methylsufonylmethane Determination by GC using Flame
 
 Ionization Mode 
 
 5.3. D-793, SOP, Cryogenic Grinding of Chewable Gels 
 
 6.0 Supplies 
 
 6.1 Chemicals: All reagents are GC grade or better. 
 
 6.1.1 MeOH 
 
 6.1.2 DGME 
 
 6.1.3 MSM reference standard 
 
 6.2 Glassware 
 
 6.2.1 HPLC vials, 12mm x 32mm with screw cap enclosures with septa
 
 6.2.2 Scintillation vials 
 
 6.2.3 Mobile phase containers 
 
 6.2.4 Volumetric glassware as required by standard and sample preparations
 
 6.3. Disposables 
 
 6.3.1 Adjustable pipette tips 
 
 6.3.2 Micro-centrifuge tubes 
 
 6.3.3. 16mL test tubes 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
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 Methylsulfonylmethane Determination by GC using | 9-768 ze 
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 Flame Ionization Detection 
 6.3.4 Disposable plastic luer lock syringe — 3mL, 6mL, or 10mL 
 
 6.3.5 Nylon syringe filters, 0.45 um 
 
 6.3.6 Weigh paper 
 
 6.4 Equipment 
 
 6.4.1 Agilent 7890 GC with headspace 
 
 6.4.2 Analytical balance 
 
 6.4.3 Ultrasonic bath 
 
 6.4.4 Vortex 
 
 6.4.5 Stir plate 
 
 6.4.6 Eppendorf centrifuge 
 
 6.4.7 Adjustable pipettes 
 
 7.0 Preparation of Diluent, Samples, and Standards 
 
 7.1. Diluent 
 
 7.1.1 Seale the Diluent preparation as required. 
 
 7.1.2 Transfer 0.60 mL of DGME to a 1-L media bottle. 
 
 7.1.3 Add 1000 mL methanol, and mix well. 
 
 Le Standard Preparation 
 
 7.2.1 Accurately weigh and transfer about 30 mg of MSM reference standard into a
 
 100-mL volumetric flask. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Riv 
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 Methylsulfonylmethane Determination by GC using 9768 
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 Flame Ionization Detection 
 7.2.2 Dissolve in and dilute to volume with Dilue nt 
 
 7.3 Sample Preparation 
 
 7.3.1 Specific sample testing details are provide] in each produ:ts profile. If a
 specific testing details section is not aviilable, then fol ov preparation
 
 procedure as described below, maintaining 20 iceritration withir tle linear range
 listed below 
 
 7.3.2 The linear range for MSM is 0.1 mg/mL —(.5 mg/ml. 
 
 7.3.3 For raw materials: weigh no less than 20 m3 inte a suitably iz:d vcbametric
 
 flask of no less than 25 mL volume to gen »ré te an analyte con:e1 tratior. that is
 
 within the validated linearity range. Dilute .o volurie with Dilu sn, and sonicate
 for 10 min. 
 
 7.3.4 For solid and liquid dose finished producti: “ombine and hon io; enize no less
 than ten dosage units. Based on the labi:l claim and fill wiigat (capsules),
 
 serving size (powders) or tablet weigkt pe’ case, ‘weigh no less 11an °C mg of
 the pooled dosages into a suitably sized voluicetric flask of no le: s than 25 mL
 
 to generate an analyte concentration that s withia the velida ed linewr range.
 
 Dilute to volume with Diluent, and sonicate fer 10 x0in. 
 
 7.3.5 For chewable gels (gummies), homogenize at least 10 dosage u tits according to
 
 the procedure outlined in D-793 Cryogenic Grinding of Chewat le Gels. Quickly
 weigh a portion of the pooled and homogenized dosages int». beaser. Use
 
 several small portions of Diluent to completely transfer the sampl: into a
 suitably sized volumetric flask to generate an analyte cone ntration that is
 
 within the validated linear range. Dilute to volume, and son:cate for 10 min.
 
 7.3.6 To manage large volumes, the sample can be initially dissolec in a smaller
 
 volume and a portion further diluted using Diluent to br nj; the analyze
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Page 
 D-768 
 Methylsulfonylmethane Determination by GC using 
 5 of 9 
 Flame Ionization Detection 
 concentration into the linear range of measurement. Equilibrate the standard
 solution to room temperature prior to performing further dilution.
 
 7.3.7 If particulates remain in the final sample preparation, a portion may be
 centrifuged at 10,000 rpm for 5 min prior to HPLC analysis. Alternatively, the
 
 sample may be filtered through a 0.45 um membrane discarding the first 3 — 4
 
 mL. 
 
 8.0 Test Conditions 
 
 8.1 Column — Phenomonex ZB-1, 0.53mm x 30m, 5um, GC column, or equivalent.
 
 8.2 Carrier gas— Helium 
 
 8.3 Inlet Liner — Restek, 4.0mm ID x 6.3mm OD x 78.5mm length straight liner with wool,
 or equivalent. 
 
 8.4 Flow Rate — 5.0mL/min 
 
 8.5 Temperature 
 
 8.5.1 Injector — 250°C 
 
 8.5.2 Column — 120°C 
 
 8.5.3 Detector — 250°C 
 
 8.6 Run Time 
 
 8.6.1 Blanks and Standards - 7 min 
 
 8.6.2 Samples - 30 min (longer may be required if samples exhibit peaks at long time)
 
 8.7 — Spit ratio - 2:1 
 
 8.8 Injection volume — 1uL 
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
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 Methylsulfonylmethane Determination by GC using D-768 
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 Flame Ionization Detection 
 8.9 Septum purge — 3 mL/min 
 
 8.10 Air flow — 400 mL/min 
 
 8.11 Hydrogen flow — 40 mL/min 
 
 8.12 Makeup flow — 30 mL/min (column + makeup = constant) 
 
 8.13 Example Sequence 
 
 8.13.1 Perform at least one injection of a Blank (Diluent). 
 
 8.13.2 Perform five injections of the Working Standard. 
 
 8.13.3 Perform a single injection of each Sample Preparation. 
 
 8.13.4 Perform a single injection of the Working Standard after every six samples and
 at the end of the run. 
 
 8.14 Retention Times 
 
 8.14.1 MSM — about 4.8 min 
 
 8.14.2 DGME - about 6.0 min 
 
 8.15 System Suitability 
 
 8.15.1 The %RSD of the peak area ratio for five injections of the Working Standard is
 NMT 2.0%. 
 
 8.15.2 The %RSD of the peak area ratio for all injections of the Working Standard is
 
 NMT 2%. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rey 
 Methylsulfonylmethane Determination by GC using D-768 2 ; 5 
 Flame Ionization Detection 
 
 9.0 Example Calculation 
 
 R, . Wiss XP . Vax... FW 
 % Label (FP) or % Assay (RM) = — xX —— ce x 100 
 Rs Viste Sply, LA 
 
 Ry Sample peak area ratio 
 
 R, Mean Working Standard peak area ratio (5 injections) 
 
 Wterq Weight of reference standard used to prepare Working Standard (mg)
 
 PF Purity of reference standard from the CoA (decimal) 
 
 Veiqg Volume of Working Standard (mL) 
 
 Vsp, Volume of Sample Solution including dilutions (mL) 
 
 Spl,,, Sample weight (mg) 
 
 FW Theoretical fill/tablet weight (mg, use 1 for raw materials) 
 
 LA Label amount (mg, use 1 for raw materials) 
 
 10.0 Example Chromatograms 
 
 10.1 Blank 
 
 Blank 
 : 
 aD. 
 OsWw 
 200 a Q 
 1507 
 < 
 100: 
 0G N» B«LeOeW 8N6 
 nL 8 ated 
 6 of 4 #46 +2 25 #8. 968 4. 461 °8 “S85. 6 65° °7 
 Time [min] 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev e 
 Methylsulfonylmethane Determination by GC using | -768 ze 5 re 
 Flame Ionization Detection 
 
 10.2 Working Standard 
 
 WSTD 19AS107 
 : : 
 
 200: % G} 
 
 ; vfoe)2 
 < 
 400; 
 505 a QE ® ” 
 Oo +O i) 
 
 0 0.5 1 1.5 2 2.5 3 3.5 4 45 5 5.5 6 7 
 Time [min] 
 
 10.3. Sample Preparation 
 
 820397 T=24m 
 A N jan} 
 200; iNx 2c= HWes 
 D 
 
 1507 
 rs 
 1005 
 KF OOOO"O |p ie] i 
 0 ‘ mn iil iid ¥ + qT T LU T qT 7 U qT T LU q qT ' y T T T Li Ul 
 
 123 45 67 8 9 1011 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
 Time [min] 
 
 
 

[SOP 

 Standard Operating Procedure SOPNo | Rev f 
 Methylsulfonylmethane Determination by GC using D-768 2 9 a 
 Flame Ionization Detection 
 
 11.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 01/02/19 | New N/A J. Maignan Added reference to validation, include linear range, simplify diluent and standard prep. Added short run time for standards and | - | - |
| 1 | 09/07/22 | blanks, add retention times and example chromatograms, update CC- system suitability and calculations. Removed “requirements” section. Removed unnecessary information and align with current SOP format. Added instruction to refer to test details for product | 22-0365 | S. Sassman |
| 2 | 05/17/23 | specific sample preparation. Added specific sample preparation CC- instruction for different dosage forms, Changed system suitability criteria from NLT 5% to NLT 2%. Changed logo. | 23-0230 | S. Sassman |