D-766

Corosolic Acid Determination by HPLC using UV-Vis Spectroscopy

Section D — Laboratory Operations and Specifications Revision 2 7 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 corosolic acid in raw materials and finished product dietary supplements using HPLC and
 
 UV/VIS spectrophotometry. 
 
 2.0 Scope 
 
 This procedure applies to the quantification and identification of corosolic acid in raw materials
 and finished products. Corosolic acid is a decent chromophore and was measured at 210, other
 
 wavelengths can be used to maximize signal to noise. 
 
 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 and Analytical Development Management to
 
 keep this procedure aligned with current practices. 
 
 4.0 Definitions 
 
 41 UV/VIS — Ultraviolet and Visible Electromagnetic Spectrums 
 
 4.2 | H3PQs — Phosphoric acid 
 
 4.3 ACN — Acetonitrile 
 
 44 CofA -— Certificate of Analysis 
 
 45 HoO- Water (> 18.2 MQ:cm) 
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev Page 
 D-766 2 of 7 
 Corosolic Acid Determination by HPLC using UV/VIS 
 Spectroscopy 
 
 46 Corosolic acid — (1S5,2R,4aS,6aR,6aS,6bR,8aR,10R,11R,12aR,14bS)-10,11-Dihydroxy-
 1,2,6a,6b,9,9, 12a-heptamethyl-2,3,4,5,6,6a,7,8,8a, 10,11,12,13,14b-tetradecahydro-1H-
 
 picene-4a-carboxylic acid 
 
 5.0 References 
 
 5.1 MV-LAB-18-206, Protocol, Corosolic Acid Determination by HPLC using UV/Vis
 
 Spectroscopy 
 
 5.2 Vijaykumar, Katta, et al. Int. J. Appl. Sci. Eng. 2006. Vol 4. Pg. 103-114.
 
 5.3. USP 43 Monograph for Banaba Leaf 
 
 6.0 Supplies 
 
 6.1 Chemicals: All reagents are HPLC grade or better. 
 
 6.1.1 H20 
 
 6.1.2 ACN 
 
 6.1.3 H3PQ4 
 
 6.1.4 Corosolic acid reference standard 
 
 6.1.5 Methanol 
 
 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. 1L Mobile Phase Container 
 
 6.2.4 50mL Volumetric Flask 
 
 6.2.5 100mL Volumetric Flask 
 
 6.3. Disposables 
 
 6.3.1 10mL Pipette Tips 
 
 6.3.2 1mL Pipette Tips 
 
 6.3.3 200uL Pipette Tips 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev Page 
 Corosolic Acid Determination by HPLC using UV/VIS | -766 | 3 of 7 
 Spectroscopy 
 
 6.3.4 1.5mL microfuge tubes 
 
 6.3.5 16mL Test Tubes 
 
 6.3.6 Disposable Plastic Luer Lock Syringe —- 3mL, 6mL, or 10mL 
 
 6.3.7 Nylon Syringe Filters, 0.45um 
 
 6.3.8 Weigh paper 
 
 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 Stir Plate 
 
 6.4.6 Eppendorf Centrifuge 
 
 6.4.7 10mL Pipette 
 
 6.4.8 ImL Pipette 
 
 6.4.9 200uL Pipette 
 
 7.0 Preparation of Mobile Phase, Dissolution Buffer, Samples, and Standards
 
 7.1 Mobile Phase A — 0.1% Phosphoric acid in H2O 
 
 Prepared by adding 1.0mL of H3PO4 to 1000mL of H20 (scale as necessary).
 
 7.2. Mobile Phase B — 0.1% Phosphoric acid in Acetonitrile 
 Prepared by adding 1.0mL of H3PO4 to 1000mL of ACN (scale as necessary).
 
 7.3 Diluent— Methanol 
 
 7.4 Standard Preparation 
 
7.4.1 The linear range of the method is 0.01 mg/mL — 0.1 mg/mL. All final standard

 and sample preparations must be within the linear range. 
 

[SOP 

 Standard Operating Procedure SOP No | Rev Page 
 Corosolic Acid Determination by HPLC using UV/VIS | D-766 | 4 of7 
 Spectroscopy 
 
 7.4.2 Use the actual purity from the CofA or the standard certification for the reference
 material for calculations. 
 
 7.4.3 The standard is prepared by weighing no less than the minimum weight of the
 analytical balance, then bringing up to the final volume in an appropriate
 
 volumetric flask using Diluent, then sonicating for 10 minutes.
 
 7.4.4 Dilutions are prepared using Diluent. Dilutions can be made using volumetric
 flasks or using 10mL, ImL, and 200uL variable pipettes. Specific standard
 
 concentrations will approximate the concentration expected to be found in the
 product being tested based on the sample dilution and calculated from the label.
 
 Dilutions can be prepared in HPLC vials. 
 
 7.5 Sample Preparation 
 
 TDI Samples can be dissolved in Diluent at any volume starting from 50mL and any
 
 weight greater than the minimum weight of the analytical balance.
 
 7.5.2 The sample is suspended in the final volume and put in the sonicator bath for at
 least 10 minutes with occasional shaking to ensure large chunks are dispersed.
 
 7.5.3 Before injection, insoluble matter should be removed via filtration using a nylon
 syringe filter. Discard at least the first 0.5mL of filtrate before collecting a sample
 
 for analysis. Dilute filtrate as needed then add 1mL of the final dilution to an
 HPLC vial for analysis. 
 
 7.5.3.1 Alternatively, samples and standards can also be centrifuged at 6,000
 
 RPM for at least 200 seconds in an Eppendorf centrifuge to pellet
 
 insoluble matter. 
 
 7.5.4 For raw materials or finished products being analyzed for the first time using this
 method, in-process verification is required to demonstrate spectral purity and
 
 extraction efficiency before the method can be implemented. 
 
 8.0 Test Conditions 
 
 8.1 Gradient (Isocratic) 
 
 Time YA %B 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev Page 
 Corosolic Acid Determination by HPLC using UV/VIS | D-766 | 5 of 7 
 
 Spectroscopy 
 
 0.00 25 75 
 
 20.0 25 75 
 
 8.2 Column — Phenomenex Luna, C18, Sum, 100A, LC column, 250mm x 4.6mm, or
 
 equivalent. 
 
 8.3 Flow Rate — 1.0mL/min 
 
 8.4 UV Detection — 210 nm 
 
 8.5 3D Spectral Range — 200 nm — 350 nm 
 
 8.6 Injection Volume - 20uL 
 
 8.7. Retention Time — about 11 minutes 
 
 8.8 | Column Temperature — Not controlled 
 
 8.9 Recommended Sequence 
 
 8.9.1 Make at least two injections of the diluent. 
 
 8.9.2 Make at least two injections of the diluent. 
 
 8.9.3 Make five injections of Standard Solution. 
 
 8.9.4 Make a single injection of each Sample Preparation. 
 
 8.9.5 Make a single injection of the Standard Solution after every six samples and at
 
 the end of the run. 
 
 8.10 System Suitability Requirements 
 
 8.10.1 The %RSD of the first five standard injections is NMT 5.0%.
 
 8.10.2 The %RSD of all injections is NMT 5%. 
 
 8.10.3 Spectral match over the range 200 nm — 350 nm is NLT 900. 
 
 8.10.4 The retention time of the sample is within 0.3 min of the standard.
 
 8.11 Column Wash and Storage 
 
 8.11.1 Wash the column with H20:ACN (25:75) at 1 mL/min for at least 15 min.
 
 8.11.2 Store the column with H2O:ACN (25:75). 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev Page 
 Corosolic Acid Determination by HPLC using UV/VIS D-766 1 6 of7 
 
 Spectroscopy 
 
 9.0 Calculations 
 
 9.1 % assay = = x “sah x —h x © x 100 
 
 Ry Sample peak area 
 
 R, Mean standard peak area 
 
 Wt..q Weight of reference standard in mg 
 
 Vstq Wolume 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. | Wolume of the sample preparation accounting for dilutions in mL
 
 SS 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. 
 
 LA Label amount in mg per dose or 1 for raw materials 
 
 10.0 Example Chromatography 
 
 10.1 Blank 
 
 Blank 
 
 80- 
 60- 
 <a 
 ¢ 40- 
 20- 
 0 aed it. AW 
 + 2» 3 4 5 6 7 8 9 10 44 #12 #13 #144 «145 16 #17 «+18 «19~«20
 Time [min] 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev Page 
 Corosolic Acid Determination by HPLC using UV/VIS | 2-766 1 7 of7 
 
 Spectroscopy 
 
 10.2 Standard 
 
 20AS021 0.07mg/mli 
 = 
 80- 
 138] 
 2 
 60- S 
 9 
 2 
 € 40- 5 
 20- 
 0 eS enn ee ee es 
 1 2 3 4 5 6 7 8 9 10 11 12 13 14 #15 16 17 18 £19 20 
 Time [min] 
 10.3 Sample 
 210177-01 0.01 mg/ml 
 80- \ 
 60- 3 
 
 ~ | | ae 
 
 i 2 3 4 5 6 7 8 § 10 11 12 13 14 #15 #16 #17 «#18 «19 = 20 
 Time [min] 
 
 11.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 01/02/19 | New N/A J. Maignan Update to reflect current practices and for clarity, add reference to l 04/15/22 method validation, add linear range, add recommended sequence, CC-22-0179 S. Sassman add system suitability requirements, add example chromatography. | - | - |