D-741

Chlorogenic Acid Determination by HPLC using UV-Vis Spectroscopy

Section D — Laboratory Operations and Specifications Revision 5 8 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 total chlorogenic acids in raw materials and finished product dietary supplements using HPLC
 
 and UV/VIS spectrophotometry. 
 
 2.0 Scope 
 
 This procedure applies to the quantification of total chlorogenic acids in raw materials and
 
 finished products. This procedure applies to the identification of chlorogenic acid forms in raw
 materials and finished products by retention time and spectral matching.
 
 3.0 Responsibility 
 
 oil It is the responsibility of QC and Analytical 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 and/or Analytical Development to
 
 keep this procedure aligned with current practices. 
 
 4.0 Definitions 
 
 4.1 QC — Quality Control 
 
 4.2 UV/VIS — Ultraviolet and Visible Electromagnetic Spectrums 
 
 4.3. ACN -— Acetonitrile 
 
 4.4 CofA — Certificate of Analysis 
 
 4.5 H20 — Water 
 
 46 CGA-Chlorogenic Acid or 3CQA or 3-O-Caffeoylquinic acid 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 : a 
 UV/VIS Spectroscopy 
 
 5.0 References 
 
 5.1 MV-LAB-14-040, Protocol, Chlorogenic acid Determination by HPLC and UV/Vis
 
 Spectroscopy 
 
 5.2 RPT-20-0044, Report, Chlorogenic Acid: Assigning 3-CQA and 5-CQA in Raw Material
 
 and Finished Products 
 3.3 TN-1134, Chlorogenic Acids from Green Coffee by HPLC, Z. Aqeel, D. Truong, J.
 
 Preston, S. Lazzaro, and S. Baugh. Joint Phenomenex and Chromadex.
 
 6.0 Supplies 
 
 6.1 Chemicals: All reagents are HPLC grade or better. 
 
 6.1.1 H20 © 18.2 MQ:cm) 
 
 6.1.2 ACN 
 
 6.1.3 Chlorogenic acid 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 Tips for adjustable pipets 
 
 6.3.2 Centrifuge tubes 
 
 6.3.3. Disposable plastic luer lock syringe —- 3mL, 6mL, or 10mL 
 
 6.3.4 Nylon syringe filters, 0.45pm 
 
 6.3.5 Weigh paper 
 6.4 Equipment 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 iz ek 
 UV/VIS Spectroscopy 
 
 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. Adjustable pipettes 
 
 7.0 Preparation of Mobile Phase, Dissolution Buffer, Samples, and Standards
 
 7.1 Mobile Phase A — 0.1% Formic acid in 25% ACN (aq) 
 
 7.1.1 Transfer 250 mL of ACN to a suitable container. 
 
 7.1.2 Add 1.0 mL of formic acid. 
 
 7.1.3 Add 750 mL of H20, and mix well. 
 
 7.2 Mobile Phase B — 0.1% Formic acid in 10% ACN (aq) 
 
 7.2.1 Transfer 100 mL of ACN to a suitable container. 
 
 7.2.2 Add 1.0 mL of formic acid. 
 
 7.2.3. Add 900ml of H20, and mix well. 
 
 7.3 Diluent-60% MeOH (aq) 
 7.3.1 Transfer 600 mL of methanol to a suitable container. 
 
 7.3.2 Add 400 ml of H20, and mix well. 
 
 7.3.3 Equilibrate to room temperature before use. 
 
 7.4 Standard Preparation 
 
 7.4.1 Accurately weigh and transfer about 25 mg of CGA reference standard into a 250-
 mL volumetric flask. 
 
 7.4.2 Dilute to volume using Diluent. 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 pun 
 UV/VIS Spectroscopy 
 
 7.4.3 Sonicate for 10 minutes or until completely dissolved. 
 
 7.5 Sample Preparation 
 
 7.5.1 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.
 
 7.5.2 The linear range of the method is 0.025 mg/mL — 0.2 mg/mL. All working sample
 
 preparations must be within this range. 
 
 7.5.3. For raw materials: Accurately weigh and transfer a portion into a suitably sized
 volumetric flask of no less than 10 mL volume to generate an analyte
 
 concentration that is within the validated linearity range. Dilute to volume with
 Diluent, and sonicate for 10 min. 
 
 7.5.4 For solid dose finished products: Combine and homogenize no less than 20
 
 dosage units. Based on the label claim and weight per dose, accurately weigh and
 transfer a portion of the homogenized sample into a suitably sized volumetric
 
 flask of no less than 10 mL to generate an analyte concentration that is within the
 
 validated linearity range. Dilute to volume with Diluent, and sonicate for 10 min.
 7.5.5 For liquid dose finished products: Use a TC pipet to transfer no less than 2.0 mL
 
 of the product into a suitably sized volumetric flask of no less than 25 mL to
 
 generate an analyte concentration that is within the validated linearity range. Wipe
 the outside of the pipet, and rinse the pipet three times with Diluent collecting the
 
 rinses in the volumetric flask. Dilute to volume using Diluent.
 
 7.5.6 For chewable gels (gummies): homogenize at least 10 dosage units according to
 the procedure outlined in D-793 Cryogenic Grinding of Chewable Gels. Quickly
 
 weigh a portion of the homogenized sample into a volumetric flask of no less than
 10 mL to generate an analyte concentration that is within the validated linearity
 
 range. Dilute to volume with Diluent, and sonicate for 10 minutes.
 
 7.5.7 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
 
 
 

[SOP 

 Standard Operating Procedure SOP No Rev 
 Page 
 Chlorogenic Acids Determination by HPLC using D-741 
 5 of 8 
 UV/VIS Spectroscopy 
 analyte concentration into the linear range of measurement. Ensure that the stock
 
 sample is equilibrated to room temperature prior to performing further dilution.
 
 7.5.8 The final sample must be filtered or centrifuged before analyzing by HPLC.
 
 7.5.8.1 For filtration: filter a portion through a 0.45um nylon membrane
 discarding the first 2-3 mL of filtrate before collecting an aliquot for
 analysis. 
 
 7.5.8.2 For centrifugation: centrifuge for 5 min at 10,000 rpm.
 8.0 Test Conditions 
 
 8.1 Gradient 
 
 Time %A %B Gradient Type 
 
 0.00 0 100 0 
 
 20.00 100 0 0 
 
 20.10 0 100 0 
 
 30.00 0 100 0 
 
 Column — Phenomenex Luna, C18 (2), 5um, 100A, 150mm x 4.6mm, or equivalent
8.2 8.3 Flow Rate — 1.0mL/min

 8.4 UV Detection — 327nm 
 8.5 Recommended 3-D Spectral Range — 200nm — 400nm 
 
 8.6 Injection Volume - 20nL 
 
 8.7 Column Temperature — 30°C 
 
 8.8 Retention Times 
 
 8.8.1 Peak 1 —4.7 min 
 
 8.8.2 CGA-—6.9 min 
 
 8.8.3 Peak 3 — 7.5 min 
 
 8.8.4 Peak 4—11.5 min 
 8.8.5 Peak 5 — 18.2 min 
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 5 ie 
 UV/VIS Spectroscopy 
 
 8.8.6 Peak 6— 19.0 min 
 
 8.8.7 Peak 7 — 20.7 min 
 
 8.9 Recommended Sequence 
 
 8.9.1 Make at least 2 injections of a Blank (Diluent). 
 
 8.9.2 Make five injections of the Working Standard. 
 
 8.9.3. Make a single injection of each Sample Preparation. 
 
 8.9.4 Make a single injection of the Working Standard after every six samples and at
 the end of the run. 
 
 8.10 System Suitability 
 
 8.10.1 The %RSD of five consecutive injections of Working Standard is NMT 5.0%.
 
 8.10.2 The %RSD of all Working Standard injections is NMT 5%. 
 
 8.11 Column Wash and Storage 
 
 8.11.1 Rinse the column with H20/ACN (50/50) at 1 mL/min for at least 15 min.
 
 8.11.2 Store the column with H20/ACN (50/50). 
 
 9.0 Calculations 
 
 x ~~ x 100 
 9.1 %assay = — x —H x 
 Ry Sample peak area for chlorogenic acid peak 
 
 Rs Mean standard peak area 
 
 Wtstq Weight of reference standard in mg 
 
 Vstq 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) 
 
 Vsp1 | Volume of the sample preparation accounting for dilutions in mL
 
 
 

[SOP 

 Standard Operating Procedure SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 7 - 
 UV/VIS Spectroscopy 
 
 5S 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 | for raw materials 
 
 10.0 Example Chromatography and Spectrum 
 
 10.1. Working Standard 
 22AS047 
 Ro} 
 3000+ < 
 2 
 c 
 25001 3 
 20004 
 = 
 ‘Bs00- 
 10004 
 500- 
 12 3 4 5 6 7 8 9 10 11 12 13 1415 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
 Time [min] 
 10.2 Sample 
 200204 
 30004 
 3 
 25001 3 
 2 
 20001 5 
 2 3 
 5004 Ss 
 — & Oo 
 10004 8 a&e ¢ !o 
 5004 ‘i i t 5 o 2 s s s « 3 a 8 
 fe) aes paws sfc aw AoNO : Tedheen TS JAKa: hcco 
 12 3 4 5 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 SOP No | Rev 
 Chlorogenic Acids Determination by HPLC using D-741 5 Page 
 8 of 8 
 UV/VIS Spectroscopy 
 
 10.3. CGA UV Spectrum 
 
 Poo Chlorogenic Acid - 7.071 (2022-05-25 19-13-59-04-00-02-r004.dx) 
 90+ f_o “t 
 804 : 2 
 70+ S 
 N 
 60; yy 
 & 504 
 407 
 30+ 
 20/ 
 107) a, . : X Se ovov. 8¥ 8v3y 
 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 
 nm 
 11.0 Revision History 

| Rev | Date | Description of Changes | CCR # | By |
|-----|----------|------------------------|-------|----|
| 0 | 12/17/14 | _ New | 14-1036 | X. Shao |
| 1 | 02/09/15 | Incorporation of validation sub-analysis for the determination of total chlorogenic acids in finished product. | 15-0105 | X. Shao |
| 2 | 01/14/19 | Scheduled review: updated format to match current Ion practices. Added example chromatography, system suitability requirements. Dt. | 19-0037 | J. Maignan |
| 3 | 06/24/21 | Strengthened SOP details. CC- | 21-0242 | J. Sassman |
| 4 | 08/05/22 | Update for consistency with current methods and lab practices, add CC- column wash and storage, edit for clarity and ease of use. Add reference to report explaining naming of CGA isomers, edit for consistency with current SOPs, add instruction to follow test ai a GaNSia details in the product profile, modify sample preparation to outline eee te Sy SenSiien specific instructions for different sample types. | 22-0335 | S. Sassman |