Analytical methods for the determination of aspirin in its combinations with clopidogrel and some statins in medications for treatment of acute coronary syndromes (ACS)

Document Type : Review Article

Author

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International University of Africa, Khartoum, Sudan

Abstract

The combination of aspirin (ASP) and clopidogrel (CLD) has demonstrated efficacy in managing coronary syndromes, including unstable angina and myocardial infarction. This regimen prevents clotting and effectively reduces the risk of vascular events by inhibiting both adenosine diphosphate and the cyclooxygenase pathway. Furthermore, cholesterol-lowering agents such as statins are also employed as a preventive measure for patients with acute coronary syndromes (ACS). This article reviews the current analytical methods for the quantitative determination of aspirin in combination with clopidogrel, or the combination of the two drugs with one of the statins, in various marketed formulations in the period of 2005 -2024. The most commonly used methods for determining these combinations include chromatographic techniques such as high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC), as well as spectrophotometric methods. Recent trends in the analysis of these combination samples show a preference for HPLC (60%), thin-layer chromatography (TLC) (22.5%) and spectrophotometric methods (17.5%) reflecting a general shift towards more sensitive methods with higher resolution capabilities. These methods also offer the advantages of requiring smaller quantities of samples and reagents and shorter analysis times.

Keywords

References

1.    Moradi O, Karimzadeh I, Davani-Davari D, Shafiekhani M, Sagheb MM. Pattern and associated factors of adherence to immunosuppressive medications in kidney transplant recipients at a referral center in Iran. Patient Prefer Adherence. 2019 May 8;13:729-738. doi: 10.2147/PPA.S198967. PMID: 31190755; PMCID: PMC6514256.
2.    Wilkins CA, Hamman H, Hamman JH, Steenekamp JH. Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features. Pharmaceutics. 2024 Jan 26;16(2):178. doi: 10.3390/pharmaceutics16020178. PMID: 38399239; PMCID: PMC10892518.
3.    Chen L, Chen J, Lu M, Stämpfli A. Simultaneous determination of elbasvir and grazoprevir in fixed-dose combination and mass spectral characterization of each degradation product by UHPLC-ESI-QTOF-MS/MS. J Pharm Biomed Anal. 2020 Jan 30;178:112964. doi: 10.1016/j.jpba.2019.112964. Epub 2019 Nov 3. PMID: 31711865.
4.    Kolansky DM. Acute coronary syndromes: morbidity, mortality, and pharmacoeconomic burden. Am J Manag Care. 2009 Mar;15(2 Suppl):S36-41. PMID: 19355807.
5.    Chaturvedula S, Diver D, Vashist A. Antiplatelet therapy in coronary artery disease: A daunting dilemma. J Clin Med 2018; 7: E74.
6.    Degrauwe S, Iglesias JF. Double antiagrégation plaquettaire pour le traitement et la prévention secondaire de la maladie coronarienne. Indications, modalités et durées de traitement [Dual antiplatelet therapy for treatment and secondary prevention of coronary artery disease: indications, modalities and duration]. Rev Med Suisse. 2016 May 25;12(520):1022-6, 1028-34. French. PMID: 27424342.
7.    Hirsh BJ, Smilowitz NR, Rosenson RS, Fuster V, Sperling LS. Utilization of and Adherence to Guideline-Recommended Lipid-Lowering Therapy After Acute Coronary Syndrome: Opportunities for Improvement. J Am Coll Cardiol. 2015 Jul 14;66(2):184-92. doi: 10.1016/j.jacc.2015.05.030. PMID: 26160634.
8.    Kamal AH, El-Malla SF, Hammad SF. A Review on UV spectrophotometric methods for simultaneous multicomponent analysis. Eur J Pharm Med Res. 2016;3(2):348-360 
9.    Lotfy HM, Saleh SS. Recent development in ultraviolet spectrophotometry through the last decade (2006–2016): A review. Int J Pharm Sci. 2016;8 (10):40-563
10.    Kale AB, Mohanty P, Choudhari VP, Sutar AS, Jagdale SC, Kuchekar BS. Spectrophotometric simultaneous determination of clopidogrel and aspirin in combined tablet dosage form by ratio derivative and area under curve method. Res J Pharm Technol. 2011;4(1):105-8.
11.    Game MD, Gabhane KB, Sakarkar DM. Quantitative analysis of clopidogrel bisulphate and aspirin by first derivative spectrophotometric method in tablets. Indian J Pharm Sci. 2010 Nov;72(6):825-8. doi: 10.4103/0250-474X.84609. PMID: 21969765; PMCID: PMC3178994.
12.    Rajput SJ, George RK, Ruikar DB. Chemometric simultaneous estimation of clopidogrel bisulphate and aspirin from combined dosage form. Indian J Pharm Sci. 2008 Jul-Aug;70(4):450-4. doi: 10.4103/0250-474X.44592. PMID: 20046769; PMCID: PMC2792539.
13.    Singh R, Khan T. Analytical method development and validation studies for the estimation of aspirin, clopidogrel bisulphate and rosuvastatin calcium in fixed dose combination (capsule) by UV spectroscopy. Indian Drugs. 2017 Jun 1;54(6).
14.    Singh S, Dubey N, Jain DK. Simultaneous estimation of atorvastatin, clopidogrel and aspirin in capsule dosage forms using UV-spectroscopy. Asian J Res Chem. 2010;3(4):885-7.
15.    Pandey S, Karmakar NK, Pandey RK, Shukla SS. A double divisor ratio-spectra derivative method for the ternary mixture of aspirin, clopidogrel bisulphate and rosuvastatin calcium. Lett Org Chem. 2021 Sep 3;11(5):696-707.
16.    Al Sawy NS, El Kady EF, Mostafa EA. A novel eco‐friendly method for simultaneous determination of aspirin, clopidogrel, and atorvastatin or rosuvastatin in their fixed‐dose combination using chemometric techniques and artificial neural networks. J Chemom. 2023 May;37(5): e3474.
17.    Issa MM, Nejem RA, Abu Shanab A, Stefan-van Staden RI. Resolution of ternary mixture of aspirin, atorvastatin, and clopidogrel by chemometric‐assisted UV spectroscopic and liquid chromatography methods. Int J Spectrosc. 2013;2013(1):726820.
18.    Sinha PK, Damle MC, Bothara KG. A validated stability indicating HPTLC method for determination of aspirin and clopidogrel bisulphate in combined dosage form. Eur J Aanal Chem. 2009 Jul 1;4(2):152-60.
19.    Patel RB, Shankar MB, Patel MR, Bhatt KK. Simultaneous estimation of acetylsalicylic acid and clopidogrel bisulfate in pure powder and tablet formulations by high-performance column liquid chromatography and high-performance thin-layer chromatography. J AOAC Int. 2008; 91(4): 750–755. https://doi.org/10.1093/jaoac/91.4.750.
20.    Gawad JB, Sugandhi GO, Bari SB. Application of HPTLC densitometric method for simultaneous quantification of rosuvastatin calcium and aspirin. Int J Pharm Biol Sci. 2013; 3(2): 173-184
21.    Tank PH, Vadalia KR, Dedania ZR. Development and validation of HPTLC method for simultaneous estimation of rosuvastatin calcium and aspirin in capsule dosage form. Int J Pharm Sci Res. 2012; 3(10): 3867-3870.
22.    Sankar AS, Shanmugasundaram P, Ravichandiran V. A robust QBD based high-performance thin-layer chromatographic method for the estimation of aspirin, clopidogrel bisulphate and rosuvastatin calcium in a pharmaceutical formulation using experimental design. Curr Anal Chem. 2017 Oct 1;13(5):386-92.
23.    The British Pharmacopoeia, HM Stationery Office, London, 2022.
24.    The United States Pharmacopoeia, The National Formulary, 43th ed., U.S. Pharmacopeial Convention, Washington, DC, 2024 electronic edition.
25.    Anandakumar K, Ayyappan T, Raghu Raman V, Vetrichelvan T, Sankar AS, Nagavalli D. RP-HPLC analysis of aspirin and clopidogrel bisulphate in combination. Indian J Pharm Sci. 2007 Jul 1;69(4):597-8.
26.    Dos B. Stability indicating RP-HPLC method for simultaneous determination of aspirin and clopidogrel in dosage form. Malaysian J Anal Sci. 2016;20(2):247-57.
27.    Gandhimathi M, Ravi TK. High Performance Liquid Chromatographic Determination of Aspirin and Clopidogrel in Tablets. Indian J Pharm Sci. 2007;69(1).
28.    Kahsay G, Lakshmi Dhulipalla R, Van Nyen G, Punie X, Van Schepdael A, Adams E. Analysis of Purity of Clopidogrel and Acetylsalicylic Acid in Combined Oral Dosage Forms. Curr Pharm Anal. 2013;9(1):82-91.
29.    Kahsay G, Van Schepdael A, Adams E. Development and validation of a liquid chromatographic method for purity control of clopidogrel-acetylsalicylic acid in combined oral dosage forms. J Pharm Biomed Anal. 2012 Mar 5;61:271-6. doi: 10.1016/j.jpba.2011.12.019. Epub 2011 Dec 23. PMID: 22226416.
30.    Kachhadia PK, Doshi AS, Joshi HS. Validated column high-performance liquid chromatographic method for determination of aspirin and clopidogrel in combined tablets in the presence of degradation products formed under ICH-recommended stress conditions. J AOAC Int. 2009 Jan-Feb;92(1):152-7. PMID: 19382573.
31.    Mahesh HR, Babu KS. A novel stability indicating HPLC assay method for simultaneous estimation of Clopidogrel and Aspirin in tablet dosage form by using core shell technology column. Res J Pharm Technol. 2015;8(2):172-6. 
32.    Sreekanth ND, Adilakshmi N. Method development and validation of aspirin and clopidogrel pharmaceutical dosage forms by developing new RP HPLC method. J Appl Pharm Res. 2020 Aug 31;8(3):38-47.
33.    Chatrabhuji PM, Pandya CV, Patel MC. Development and validation of RP-HPLC-UV method for simultaneous quantitation of clopidogrel bisulphate and aspirin in bulk drug. Anal  Chem. 2014;15(2):43-8.
34.    Usman S, Akram M, Shah F, Ramesh KV, Islam Q. Stability Indicating HPLC Method for Simultaneous Assessment of Clopidogrel Bisulfate and Aspirin: Development and Validation. Int J Pharm Investigation. 2023 Apr 1;13(2):270-278.
35.    Rashad EA, Elsayed SS, Nasr JJ, Ibrahim FA. Factorial design optimized green reversed-phase high-performance liquid chromatography for simultaneous determination of aspirin and clopidogrel in pharmaceutical tablets. Microchem J. 2023; 190:108610.
36.    Gandla K, Lalitha R, Kishore K, Gopikrishna R. A validated RP-HPLC method for simultaneous estimation of aspirin and rosuvastatin in tablet dosage form. International Journal of Pharma and Chemical Research. 2015 Jul;1(3):128-33.
37.    Panda SS. Ion-pairing RP-HPLC method for simultaneous determination of aspirin and clopidogrel bisulphate in tablet and capsule dosage form. Int J Pharmtech Res. 2010;2(1):269-73.
38.    Shrivastava PK, Basniwal PK, Jain D, Shrivastava SK. Concurrent Estimation of Clopidogrel Bisulfate and Aspirin in Tablets by Validated RP-HPLC Method. Indian J Pharm Sci. 2008 Sep;70(5):667-9. doi: 10.4103/0250-474X.45414. PMID: 21394272; PMCID: PMC3038300.
39.    Shah DA, Bhatt KK, Mehta RS, Shankar MB, Baldania SL, Gandhi TR. Development and Validation of a RP-HPLC Method for Determination of Atorvastatin Calcium and Aspirin in a Capsule Dosage Form. Ind J Pharm Sci. 2007;69(4).:546-549.
40.    Panchal A, Sanghvi G, Vachhani A, Sheth N, Vaishnav D. Simultaneous determination of aspirin and rosuvastatin calcium in capsules by using RP-HPLC coupled with photo diode array detection. International Letters of Chemistry, Physics and Astronomy. 2014;14(2):218-30.
41.    Dumasiya MR, Bhatt KK, Patel B, Joshi NK. Development and validation of stability indicating RPHPLC method for estimation of rosuvastatin calcium and aspirin in combined dosage form. Pharma Science Monitor. 2012 Nov 1;3(4).2421-2439.
42.    Solanki CH, Patel NI. Development and validation of RP-HPLC method for simultaneous estimation of rosuvastatin calcium and aspirin in capsule dosage form. Int J Pharm Bio Sci. 2012;3(3):577-85.
43.    Sultana N, Arayne MS, Ali KA, Nawaz M. Simultaneous determination of clopidogrel and aspirin by RP-HPLC from bulk material and dosage formulations using multivariate calibration technique. J Chromatogr Sci. 2011 Feb;49(2):165-9. doi: 10.1093/chrsci/49.2.165. PMID: 21223644.
44.    Spiridon AM, Neamtu J, Belu I, Turcu-Stiolica TS, Croitoru O. Simultaneous Analysis of Clopidogrel Bisulfate, Acetylsalicylic Acid and Atorvastatin calcium in Tablets by HPLC Method. Curr Health Sci J. 2015 Apr-Jun;41(2):172-178. doi: 10.12865/CHSJ.41.02.13. Epub 2015 Apr 10. PMID: 30364896; PMCID: PMC6201208.
45.    Pisal PO, Nigade GA, Kale AM, Pawar SM. Development and validation of stability indicating RP-HPLC method for simultaneous determination of aspirin, rosuvastatin, clopidogrel in bulk and pharmaceutical dosage form. Int J Pharm Pharm Sci. 2018 Oct 1;10(10):51-6.
46.    Tiwari PK, Jain A, Dubey BK, Pandey GK, Dhakad S. Analytical method development and validation for the simultaneous estimation of aspirin, clopidogrel and rosuvastatin in pharmaceutical dosage form. J Drug Del Ther. 2019 Aug 15;9(4-s):432-8.
47.    Sundar RS, Valliappan K. An improved RP-HPLC method for the simultaneous estimation of aspirin, atorvastatin, and clopidogrel in pharmaceutical formulation using experimental design methodology. Int J Pharm Pharm Sci. 2014; 6:279-83.
48.    Londhe SV, Deshmukh RS, Mulgund SV, Jain KS. Development and Validation of a Reversed-phase HPLC Method for Simultaneous Determination of Aspirin, Atorvastatin Calcium and Clopidogrel Bisulphate in Capsules. Indian J Pharm Sci. 2011 Jan;73(1):23-9. doi: 10.4103/0250-474X.89753. PMID: 22131618; PMCID: PMC3224406.
49.    Mostafa EA, El‐Ashrey MK, Mahmoud ST. An innovative combination of Box-Behnken design and ecofriendly approaches for the simultaneous determination of aspirin, clopidogrel, atorvastatin and rosuvastatin in their fixed-dose combination tablets. BMC chemistry. 2023 Nov 24;17(1):164. 
50.    Devika GS, Sudhakar M, Rao JV. A new simple RP-HPLC method for simultaneous estimation of asprin, atorvastatin and clopidogrel in capsule dosage form. Asian J Res Chem. 2011;4(5):795-9.
51.    Elkady EF, Tammam MH, El maaty AA. Stability indicating HPLC-UV vs. UPLC-DAD for estimation of atorvastatin simultaneously with aspirin, clopidogrel and their related impurities in bulk and capsules. Anal Chem Lett. 2017 Sep 3;7(5):596-610.
52.    Dubey N, Patel M, Jain DK. Simultaneous estimation of aspirin, atorvastatin and clopidogrel in combined capsule dosage form using reverse phase high-performance liquid. Int J Res Pharm Biomed Sci. 2013; 7:42-44.
53.    Sathiyasundar R, Valliappan K. New stability indicating assay method by liquid chromatographic separation of aspirin, atorvastatin and clopidogrel in pharmaceutical dosage form. Indo Am J Pharm Res. 2014; 4(12):5919 -5927.
54.    Validation of analytical procedures: Text and methodology. CPMP/ICH/381/95. June 1995.http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002662.pdf Accessed on 31st May 2024.
55.    Elder DP, Borman P. Improving analytical method reliability across the entire product lifecycle using QbD approaches. Pharm Outsourcing.  August 7, 2013 Accessed on 31st May 2024.
Trends in Pharmaceutical Sciences
Volume 10, Issue 2
June 2024
Pages 165-180

Files

Share

How to cite

Statistics