D-780

Determination of Quercetin by HPLC using UV-Vis Spectroscopy

Section D — Laboratory Operations and Specifications Revision 3 7 pages

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1.0 Purpose 
 
 This document describes the analytical procedure for the determination of Quercetin in raw
 
 materials and finished products. 
 
 2.0 Scope 
 
 This procedure applies to the identification and quantification of Quercetin in raw materials and
 
 finished products in the QC laboratory at Ion Labs. 
 
 3.0 Responsibility 
 
 3.1 It is the responsibility of QC and Analytical chemists who have verified their ability to
 
 execute this procedure to follow this procedure. 
 
 It is the responsibility of QC Laboratory Management to implement this procedure and
 a2 
 to ensure that the procedure is being followed. 
 It is the responsibility of QC Laboratory Management and/or Analytical Development to
3.3 keep this procedure current with the associated monographs and laboratory practices.

 4.0 Definitions 
 
 4.1 QC — Quality Control 
 
 4.2 AD-—Analytical Development 
 
 4.3. H3PO«4-— Phosphoric Acid 
 
 4.4 MeOH — Methanol 
 
 4.5 HPLC — High Performance Liquid Chromatography 
 
 4.6 UV/Vis — Ultraviolet & Visible Electromagnetic Spectra 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Determination of Quercetin by HPLC using UV/Vis D-780 3 Page 2 of 7 
 
 Spectroscopy 
 
 5.0 References 
 
 5.1 MV-LAB-19-118, Protocol, Quercetin Determination Using HPLC with UV/Vis
 Spectroscopy 
 
 5.2 RPT-21-0026, Report, Estimation of Uncertainty 
 
 6.0 Reagents, Supplies, Glassware, and Equipment 
 
 6.1 Chemicals — All reagents are HPLC grade or better 
 
 6.1.1 Milli-Q Water 
 
 6.1.3 MeOH 
 
 6.1.4 H3PO4 
 
 6.1.4 Quercetin Reference Standard 
 
 6.2 Supplies and Glassware 
 
 6.2.1 HPLC vials, 12mm X 32mm with screw cap enclosures w/ septa 
 
 6.2.2 Volumetric glassware and/or adjustable pipettes and tips 
 
 6.2.3 Weigh paper or funnels 
 
 6.2.4 10ml Syringes with 17mm x 0.45u Nylon Syringe Filters 
 
 6.3. Equipment 
 
 6.3.1 Suitable gradient HPLC system consisting of a pump, autosampler, column oven
 
 and UV detector with a chromatographic data handling system 
 
 6.3.2 Analytical Balance 
 
 6.3.3. Sonicator bath 
 
 6.3.4 Wrist Action Shaker 
 
 7.0 Procedure 
 
 Pod Mobile Phase & Diluent Preparation 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Determination of Quercetin by HPLC using UV/Vis D-780 3 Page 3 of 7 
 Spectroscopy 
 
 7.1.1. Mobile Phase 
 7.1.1.1. Combine 500 mL of MeOH, 500 mL of Milli-Q Water and SmL of
 
 H3P04. Mix well. 
 
 7.1.2 Diluent 
 
 7.1.2.1 MeOH. 
 
 7.1.3. Preparations may be scaled as necessary. 
 
 7.2 Standard Prep 
 
 7.2.1 Stock Std A: Accurately weigh and transfer about 20 mg of Quercetin reference
 
 standard into a 100-mL volumetric flask. Add 50mL of MeOH. Shake
 mechanically for 10min then sonicate for 5min. Let cool to ambient then dilute
 
 to volume with MeOH and mix well. 
 
 7.2.2. Working Std A: Transfer 5.0 mL of Stock Std A to a 50-mL volumetric flask.
 
 Dilute to volume with MeOH. 
 
 7.2.3. Prepare a second standard, Std B, as a standard recovery check.
 
 7.3. Sample Preparation 
 
 7.3.1 Specific sample testing details are provided in each products profile. If a specific
 testing details section is not available, then follow preparation procedure as
 
 described below, maintaining concentration within the linear range listed below.
 
 7.3.2 The validated range for the analytical method is 2 - 93 g/mL.
 
 7.3.3 For finished products, if not a powder, at least 10 dosage units are pooled and
 
 ground by mortar and pestle. Based on the dosage weight (for powders), fill
 weight (for capsules) or tablet weight per dose and the label claim, weigh no less
 
 than 190 mg of the pooled dosages into a suitably sized volumetric flask to
 generate an analyte concentration that is within the validated linearity range for
 
 the analyte being tested. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 
 Determination of Quercetin by HPLC using UV/Vis D-780 3 Page 4 of 7 
 Spectroscopy 
 
 7.3.4 Prepare raw materials like standards. (However, be sure to consult the
 
 specification for expected potency, as raw material samples may not be 100%.)
 
 730 Samples can be dissolved in MeOH at any volume starting from 50mL. The
 
 volume chosen must be in the solubility range of Quercetin (validated at 0.25
 mg/ml). 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. 
 
 T36 Fill the flask to about 70% of the calculated volume with MeOH and shake
 mechanically for 10 minutes. Sonicate for 10 minutes, cool to room temperature
 
 and bring up to volume with MeOH. Filter a portion for use in subsequent
 dilutions. 
 
 del Perform further dilutions as required using MeOH. 
 
 Note: Sample preparations must be injected on the same day as the preparation.
 Degradation of Quercetin may occur in extended hold times. 
 
 TA HPLC Parameters 
 
 7.4.1 Column: Agilent InfinityLab Poroshell 120 EC-C18, 4.6 x 100mm, 2.7u or
 
 equivalent 
 
 7.4.2 Column Temperature: 30°C 
 
 7.4.3 Flow rate: 0.7 mL/min 
 
 7.4.4 Wavelength: 370 nm 
 
 7.4.5 Injection Volume: 5 wL 
 
 7.4.6 Run Time: 15 minutes. 
 
7.4.7 Recommended 3-D Spectral Range (for Identification) - 220nm to 400nm

 7.5 Recommended Sequence 
 
 7.5.1 Make at least 2 injections of the diluent. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 D-780 
 Determination of Quercetin by HPLC using UV/Vis Page 5 of 7 
 Spectroscopy 
 7.5.2 Make five (5) injections of Working Std A. 
 
 7.5.3 Make two (2) injections of Working Std B. 
 
 7.5.4 Make a single injection of each Sample Preparation. 
 
 7.5.5 Make a single injection of Working Std A after every ten (10) sample injections
 or at the end of a run. 
 
 7.6 System Suitability Requirements 
 
 7.6.1. The %RSD of the first five (5) standard injections is NMT 2.0%
 
 7.6.2 The % recovery of Working Standard A, using Working Standard B is 98-102%.
 
 7.6.3 The %RSD of all Working Std A injections is NMT 3%.If present, any
 
 interference in the diluent should be subtracted out of the sample and standard
 
 peak areas. 
 
 7.7 Example calculations for determining finished product % label or raw material % purity
 
 7.7.1 % Querceti; n = —Ru x., —Wtst=axP .x, =SS Ka Vs e pl x 100 
 Rs Vsta SA 
 
 By Sample peak area 
 
 Rs Mean standard peak area 
 
 Wtsta Weight of the reference standard in mg 
 
 Veta 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) 
 
 Veni Volume of the sample preparation accounting for dilutions in mL
 
 Ae) Serving size: Average weight of ten dosage units in mg for tablets, fill
 
 weight for capsules, mass of a single serving in mg for powders,
 volume of a single serving from the theoretical formula in mL for
 
 liquids, or 1 for raw materials. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Determination of Quercetin by HPLC using UV/Vis D-780 3 Page 6 of 7 
 
 Spectroscopy 
 
 LA Label amount in mg of Quercetin (use 1 for raw materials)
 
 7.8 Reporting Results 
 7.8.1 The expanded uncertainty of the method is 1.1% with a coverage factor of 2.
 
 72 Results should include the expanded uncertainty of the method along with the
 
 coverage factor in the following format: 
 
 78.2.1 102% of Label Claim, U=+1.1% k=2 
 
 7.9 Column Wash and Storage 
 
 7.9.1 Wash and store the column in 50:50 MeOH/ Milli-Q Water. 
 
 8.0 Chromatograms 
 
 8.1 Typical Diluent Chromatogram 
 
 Blank 
 20+ 
 18+ 
 164 
 14+ 
 5 12+ 
 <x 104 
 E 3 
 64 
 44 
 24 
 “ 0 24 4 : 2 + 3 a 4 . 5 . 6 : £ 8 : 9 . 1 : 0 1 . 1 2 . 1 = 3 1 ‘ 4 1 , 5
 Time [min] 
 8.2 Typical Working Standard Chromatogram 
 22AS061 A 
 = 
 22 
 20+ 8 
 ao 
 18+ 
 164 
 144 
 > 124 
 = 104 
 84 
 64 
 434 | 
 1 2 3 4 5 6 7 8 9 10 14 12 13 14 15 
 Time [min] 
 
 

[SOP 

 Standard Operating Procedure SOPNo | Rev 
 Determination of Quercetin by HPLC using UV/Vis D-780 3 Page 7 of 7 
 Spectroscopy 
 
 8.3. Typical Sample Chromatogram 
 
 230057 
 55 = 
 50+ a8 
 45+ Po 
 40+ 6 
 35+ 
 > 30+ 
 = 25 
 20+ 
 154 
 10; 
 54 
 : Vv 
 1 2 3 4 5 6 7 8 9 io 4% 2 15 
 Time [min] 
 
 9.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 06/26/19 | New. N/A C. Perry | - | - |
| 1 | 11/09/21 | Updated for ISO 17025 requirements. CC- Change Std B prep to be separate weigh off, add instruction to | 21-0426 | J. Sassman |
| 2 | 02/23/23 | enecls the product profile for test details, remove language CC- requiring in-process validation for new products, make chromatograms look better, correct the linear range. | 23-0093 | S. Sassman |
| 3 | 12/12/23 | Added statement regarding sample stability. CC- | 23-0598 | J. Sassman |