D-753

Diindoylmethane Determination by HPLC coupled with UV-VIS Spectroscopy

Section D — Laboratory Operations and Specifications Revision 3 7 pages

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1.0 Purpose 
 
 The purpose of this procedure is to describe a method for the quantitative analysis and
 
 identification of diindoylmethane in raw materials and finished products using HPLC and
 
 UV/VIS spectrophotometry. 
 2.0 Scope 
 
 This procedure applies to the quantification and identification of diindoylmethane in the QC
 
 laboratory at Ion Labs. Diindoylmethane was quantified at 280 nm. Other wavelengths can be
 
 used with justification if interferences are present.. 
 
 3.0 Responsibility 
 
 a1 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 to
 
 keep this procedure aligned with current Ion Labs practices. 
 
 4.0 Definitions 
 
 4.1 ACN — Acetonitrile 
 
 4.2 QC — Quality Control 
 4.3 CofA — Certificate of Analysis 
 
 4.4 H20 — Water 
 
 5.0 References 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 | Page 2 of 7 
 
 UV/VIS Spectroscopy 
 
 5.1 MV-LAB-18-066, Protocol, Diindoylmethane Determination using HPLC with UV/VIS
 Spectroscopy 
 
 6.0 Reagents, Supplies, Glassware and Equipment 
 
 6.1 Reagents: all reagents are HPLC grade or better. 
 
 6.1.1 HoO © 18.2 MQ-cm) 
 
 6.1.2 ACN 
 
 6.1.3 Diindoylmethane reference standard 
 
 6.2 Glassware 
 
 6.2.1 HPLC vials, 12mm X 32mm with screw cap enclosures w/ septa 
 
 6.2.2 Mobile Phase Bottles 
 6.2.3. Volumetric Flasks 
 
 6.2.4 Volumetric Pipets 
 
 6.3. Disposables 
 
 6.3.1 Pipet Tips 
 
 6.3.2 Microcentrifuge Tubes 
 
 6.3.3 Plastic Luer Lock Syringe 
 
 6.3.4 0.2 or 0.45um Nylon syringe filters 
 
 6.3.5 Weigh Paper or Weigh Boats 
 
 6.4 Equipment 
 6.4.1 Suitable gradient HPLC system consisting of a pump, autosampler, column oven
 
 and UV detector with a chromatographic data handling system 
 
 6.4.2 Analytical Balance 
 
 6.4.3. Ultrasonic Bath 
 
 6.4.4 Vortex 
 
 6.4.5 Eppendorf Centrifuge 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 Page 3 of 7 
 
 UV/VIS Spectroscopy 
 
 6.4.6 Adjustable Pipets 
 
 7.0 Preparation of Mobile Phase, Diluent, Standards, and Samples 
 
 7.1 Mobile Phase A — H20 
 
 7.2 Mobile Phase B-— ACN 
 7.3. Diluent — Methanol 
 
 7.4 Stock Standard Preparation 
 
 7.4.1. Accurately weigh and transfer about 25 mg of reference standard into a 100-mL
 
 volumetric flask. 
 
 7.4.2. Dissolve in and dilute to volume using Diluent. 
 7.5. Dissolve in and dilute to volume using Diluent.Working Standard Preparation
 
 7.5.1. Transfer 5.0 mL of Stock Standard into a 50-mL volumetric flask.
 
 7.5.2 Dilute to volume using Diluent. 
 7.5.3. Alternate standard preparations are acceptable provided that the working
 standard concentration is within the linear range listed below.
 
 7.6 Sample Preparation 
 
 7.6.1 Specific sample testing details are provided in each products profile. Ifa specific
 testing details section is not available, then follow preparation procedure as
 
 described below, maintaining concentration within the linear range listed below.
 
 7.6.2 The linear range of the method is 0.01mg/mL to 0.lmg/mL. All standard and
 sample preparations must be within the linear range of the method.
 
 7.6.3 For finished products, at least 10 dosage units are pooled and ground by mortar
 
 and pestle as necessary. 
 
 7.6.4 Based on the label claim and fill or tablet weight per dose for finished products
 or expected potency for raw materials, weigh a portion of the sample into a
 
 suitably-sized volumetric flask to generate an analyte concentration that is
 
 within the validated linear range for the analyte being tested.
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 Page 4 of 7 
 
 UV/VIS Spectroscopy 
 
 7.6.5 Samples can be dissolved in Diluent at any volume. Suspend the sample in 2/3
 flask volume of Diluent and shake mechanically for 20 minutes. Dilute to
 
 volume using Diluent. 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. The final diluted sample must be filtered or centrifuged before
 
 analyzing by HPLC. 
 
 7.6.6 For filtration, using the final diluted sample withdraw up to 10mL using a 10mL
 
 plastic syringe then filter and discard at least 0.5mL of filtrate before collecting
 a portion for analysis. From the collected sample dilute as needed then add
 
 sample to an HPLC vial for analysis. 
 
 7.6.7 For centrifugation using the final diluted sample, fill an even number of 1.5mL
 or 2.0mL micro centrifuge tubes and pellet out insoluble matter for 5 minutes at
 
 6000rpm. 
 
 8.0 Test Conditions 
 
 8.1 Gradient-multistep 
 
 Time YA %B 
 
 0.00 98 2 
 
 1.00 98 2 
 
 2.00 80 20 
 3.00 80 20 
 
 4.00 69 31 
 
 6.00 69 31 
 
 7.00 55 45 
 
 8.00 45 55 
 
 10.0 45 55 
 
 11.0 35 65 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 Page 5 of 7 
 
 UV/VIS Spectroscopy 
 
 11.1 98 Z 
 
 15.0 98 2 
 8.1.1 Column- Symmetry300 C18, 3.5, 4.6 X 75mm 
 
 8.1.2 Flow Rate- 1.0mL/min 
 
 8.1.3 UV detection- 280nm 
 
 8.1.4 Injection volume- 20uL 
 
 8.1.5 | Column Temperature- 45°C 
 
 8.1.6 Recommended 3-D Spectral Range- 200nm to 350nm 
 
 8.2 Sequence 
 
 8.2.1 Make at least 2 injections of a Blank (Diluent). 
 
 8.2.2 Make five injections of the Working Standard. 
 
 8.2.3 Make a single injection of each Sample Preparation. 
 8.2.4 Make a single injection of the Working Standard after every six samples and at
 
 the end of the run. 
 
 8.3. System Suitability 
 
 8.3.1 The %RSD of five consecutive injections of Working Standard is NMT 5.0%.
 
 8.3.2 The %RSD of all Working Standard injections is NMT 5%. 
 
 8.4 Column Wash and Storage 
 8.4.1 Rinse the column 100% ACN at 1 mL/min for at least 10 min. 
 
 8.4.2 Store the column with 100% ACN. 
 
 9.0 Example Calculation 
 
 9.1 % assay = au 5 aWtctq XP x —V E x=SS x 100 
 
 Ry Sample peak area 
 
 Rs Mean standard peak area 
 
 Wtgiqg Weight of reference standard in mg 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 Page 6 of 7 
 
 UV/VIS Spectroscopy 
 
 Veeq Volume of the standard preparation accounting for dilutions in mL
 
 P Purity of the reference standard in decimal format 
 
 SA Sample amount in mg (solids) or mL (liquids) 
 Vsn. | Volume of the sample preparation accounting for dilutions in mL
 
 So Serving size: Weight of a single dosage unit in mg for tablets and capsules,
 
 volume of a single serving from the theoretical formula in mL for liquids, or 1 for
 
 raw materials. 
 
 9.2 LA Label amount in mg per dose or 1 for raw materialsExample Chromatography
 
 10.0 Example Chromatography 
 
 10.1 Standard Injection 
 
 22AS035 0.05MG/ML 
 350 
 250-4 
 = 200+ 
 150- 
 700- 
 50-4 
 4 2 3 4 5 6 7 8 9 10 41 12 13 14 15 
 Time [min] 
 
 10.2. FP Sample Injection 
 220099 
 350- *~ 4 
 300- | Sots acer 
 DIM 
 250- 
 ~ 200+ la.021 
 150- 
 100- 
 = $2201.103 B-SOPL gz0s6.2537.575 i 
 4 2 3 4 5 6 7 8 9 410 11 12 13 14 15 
 Time [min] 
 10.3. Example Spectrum for DIM 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Diindoylmethane Determination by HPLC using D-753 3 Page 7 of 7 
 
 UV/VIS Spectroscopy 
 
 100 seh 
 20+ oN 
 ff \ 
 = 50~ \ 
 7 \ —— NN 
 
 11.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 06/06/18 | New procedure. N/A J. Maignan aCe M ad i d n i o t r io c n l a a l r i d f e i t c a a i t l i s o n t s o . t e A st d m d e e t d h o e d x . a mple chromatography and sik cai $, Sassngn Update for consistency with current methods and lab practices, | - | - |

 2 ee w a i d t d h r s e y c s o t m e m m e s n ui d t e a d bi l s i e t q y u s e e n c c t e io s n e , c a ti d o d n , c r o e l p u l m a n ce w r a e s q h u i a r n e d m e s n t t o s ra ge, Ce : eae tal
 make example chromatography easier to read. 
 Simplify standard preparation, add instruction to check the 
 3 02/23/23 | product profile for test details, remove language requiring in- CC-23-0096 S. Sassman
 process validation for new products.