Skip to main content
SpringerLink
Log in

Two validated stability-indicating chromatographic methods for the separation of two anti-hypertensive combinations in the presence of their degradation products or impurities

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

Two RP-HPLC methods were developed, optimized, and validated for the determination of two different anti-hypertensive combinations in the presence of their degradation products or impurities and in their pharmaceutical formulations. The first mixture is Ramipril (RAM) in combination with Amlodipine besylate (AML) [mixture I], while the second one is a combination of Ramipril (RAM), Atorvastatin (ATV), and Aspirin (ASP) [mixture II].The proposed combinations were successfully separated on X-bridge C18column (250 × 4.6 mm i.d, 5 µm p.s.), using a mobile phase of 0.05 M phosphate buffer-acetonitrile-THF (60:40:0.1% by volume) pH 2.5 and an isocratic mobile phase formed of acetonitrile-0.05 M phosphate buffer-THF (60:40:0.1% by volume) pH 2.5 for mixture (I) and (II) at a flow rate of 1 mL/min and 1.2 mL/min, respectively. The compromising components of the mixtures were detected at 218 nm. For the best separation of the mentioned components different parameters were examined and optimized. The two suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of the cited components in presence of their obtained degradation products as well as in their commercial pharmaceutical formulations. For both methods the obtained results were statistically analyzed and compared to those of the official and reported methods; using Student’s t test and F test showing no significant difference with high accuracy and good precision.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aschar GD, Oliveira L, Cesar P, Rosa P (2015) The degradations routes of Ramipril and its products. Am J Pharmatech Res 5(2):81–94

    CAS  Google Scholar 

  • Babu KA, Kumar GV, Sivasubramanian L (2011) Simultaneous estimation of ramipril and amlodipine in bulk and tablet dosage form by RP-HPLC method. Int J Pharm Pharm Sci 3(4):196–198

    Google Scholar 

  • British Pharmacopoeia, Medicines and Healthcare Products Regulatory Agency (MHRA), London 2013

  • Brunton LL, Lazo JS, Parker KL (2006) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York

    Google Scholar 

  • Dai SY, Qiu ST, Wu W, Fu CM (2013) Development and validation of an rp-hplc method for simultaneous determination of Ramipril and Amlodipine in tablets. J Pharm Anal 3(6):440–446. https://doi.org/10.1155/2014/874587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Darwish HW, Hassan SA, Salem MY, El-Zeany BA (2016) Advanced stability indicating chemometric methods for quantitation of amlodipine and atorvastatin in their quinary mixture with acidic degradation products. Spectrochimica Acta—Part A: Mol Biomol Spectrosc 154:58–66. https://doi.org/10.1016/j.saa.2015.10.007

    Article  CAS  Google Scholar 

  • De Diego M, Godoy G, Mennickent S, Olivares M, Godoy R (2010) Stress degradation studies of ramipril by a validated stability-indicating liquid chromatographic method. J Chil Chem Soc 55(4):450–453. https://doi.org/10.4067/S0717-97072010000400008

    Article  Google Scholar 

  • Elshanawane AA, Mostafa SM, Elgawish MS (2008) Application of a validated, stability-indicating LC method to stress degradation studies of Ramipril and Moexipril. HCl Chromatographia 67(7/8):567–573. https://doi.org/10.1365/s10337-008-0544-3

    Article  CAS  Google Scholar 

  • Evoy GKM (2009) AHFS Drug Information, American Society of Health-System Pharmacists, Bethesda, pp 2016–2019

  • Gajula R, Pilli NR, Ravi VB, Maddela R, Inamadugu JK, Polagani SR, Busa S (2012) Simultaneous determination of atorvastatin and aspirin in human plasma by LC-MS/MS: its pharmacokinetic application. Sci Pharm 80(4):923–940. https://doi.org/10.3797/scipharm.1206-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta KR, Wankhede SB, Tajne MR, Wadodkar SG (2007) Simultaneous determination of Amlodipine and Ramipril by high performance thin layer chromatography. Asian J Chem 19(6):4177–4182

    CAS  Google Scholar 

  • Hassan SA, Elzanfaly ES, Salem MY, ElZeany AB (2016) Development and validation of HPLC and CE methods for simultaneous determination of amlodipine and atorvastatin in the presence of their acidic degradation products in tablets. Acta Parm 66:479–490. https://doi.org/10.1515/acph-2016-0040

    Article  CAS  Google Scholar 

  • ICH, Q1A (R2) (2003) Stability testing of new drug substances and products. International Conference on Harmonization, IFPMA, Geneva, Switzerland

  • Kumar AM, Kumar PV, Nasare M, Rao V, Parasad VVL, Diwan VP (2012) Isocratic RP-HPLC estimation of Ramipril and Amlodipine in pharmaceutical dosage form. J Adv Pharm Educ Res 2(3):137–145

    Google Scholar 

  • Martindale (2003) The complete drug reference; Pharmaceutical Press: London, 33rd edition. 966

  • Maste MM, Kalekar MC, Kadian N, Bhat AR (2011) Development and validation of RP-HPLC method for simultaneous estimation of Amlodipine and Ramipril in bulk and tablet dosage form. Asian J Res Chem 4(8):1210–1213

    Google Scholar 

  • Moffat AC, Osselton MD, Widdop B (2011) Clarke’s analysis of drugs and poisons. Pharmaceutical Press, London

    Google Scholar 

  • Panchal HJ, Suhagia BN, Patel NJ, Rathod IS, Patel BH (2009) Simultaneous estimation of Atorvastatin Calcium, Ramipril and Aspirin in capsule dosage form by RP-LC. Chromatographia 69(1–2):91–95. https://doi.org/10.1365/s10337-008-0831-z

    Article  CAS  Google Scholar 

  • Patel J, Patel M (2014) RP-HPLC method development and validation for the simultaneous estimation of ramipril and amlodipine besylate in capsule dosage form. J Chem Pharm Res 6(6):725–733

    CAS  Google Scholar 

  • Patil PR, Rakesh SU, Dhabale PN, Burade KB (2009) Simultaneous estimation of ramipril and amlodipine by UV spectrophotometric method. Res J Pharm Technol 2(2):304–307. http://www.indianjournals.com/ijor.aspx?target=ijor:rjpt&volume=2&issue=2&article=017

  • Patole SM, Khodke AS, Potale LV, Damle MC (2010) A validated HPLC method for analysis of atorvastatin calcium, ramipril and asprin as the bulk drug and in combined capsule dosage forms. Int J Pharm Sci Rev Res 4(3):40–45. www.globalresearchonline.net

  • Rajput PS, Kaur A, Gill NK, Mittal K, Sarma GS (2012) Simultaneous estimation of ramipril and amlodipine in bulk and tablet dosage form by RP-HPLC method. J Appl Pharm Sci 2(7):160–165. https://doi.org/10.7324/japs.2012.2724

    Article  Google Scholar 

  • Ramadevi K, Saraswathi Z, Maniklal D (2013) RP-HPLC method development for simultaneous determination of the drugs Ramipril and Amlodipine. IJSR 2(2):4–7. https://doi.org/10.15373/22778179/FEB2013/123

    Article  Google Scholar 

  • Sankar ASK, Vetrichelvan T, Venkappaya D, Nagavalli D (2011) Simultaneous estimation of Ramipril, Aspirin and Atorvastatin Calcium by classical least squares regression in capsule dosage form. Res J Pharm Technol 4(3):398–401. https://www.researchgate.net/publication/286696813_Simultaneous_estimation_of_ramipril_aspirin_and_atorvastatin_calcium_by_classical_least_squares_regression_in_capsule_dosage_form

  • Sankar ASK, Vetrichelvan T, Venkappaya D (2011b) Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules. Acta Pharmaceutica 61(3):283–296. https://doi.org/10.2478/v10007-011-0027-1

    Article  CAS  PubMed  Google Scholar 

  • Sharma R, Khanna S, Mishra GP (2012) Development and validation of RP-HPLC method for simultaneous estimation of Ramipril, aspirin and Atorvastatin in pharmaceutical preparations. E-J Chem 9(4):2177–2184. https://doi.org/10.1155/2012/891695

    Article  CAS  Google Scholar 

  • Shetty SK, Surendranath KV, Radhakrishnanand P, Borkar RM, Devrukhakar PS, Jogul J, Tripathi UM (2011) Stress degradation behavior of a polypill and development of stability indicating UHPLC method for the simultaneous estimation of aspirin, atorvastatin, ramipril and metoprolol succinate. Am J Anal Chem 2:401–410. https://doi.org/10.4236/ajac.2011.24049

    Article  CAS  Google Scholar 

  • Snyder LR, Kirkland JJ, Dolan JW (2011) Introduction to liquid chromatography, 3rd edn. Wiley, London

    Google Scholar 

  • United States Pharmacopeia (2007) 30th edition. U.S. Pharmacopeial Convention Rockville, MD

    Google Scholar 

  • The Merck index, An encyclopedia of chemicals, drugs and biological, 13th Merck Research

  • Zaazaa HE, Abbas SS, Essam HAM, El-bardicy MG (2012) Validated chromatographic methods for determination of perindopril and amlodipine in pharmaceutical formulation in the presence of their degradation products. J Chromatogr Aphic Sci 51:533–543. https://doi.org/10.1093/chromsci/bms171

    Article  CAS  Google Scholar 

  • Zoglio MA, Maulding HV, Haller RM, Briggen S (1986) Inhibition of stearate lubricant induced degradation of aspirin by the use of certain organic acids. J Pharm Sci 57:1877–1880. https://doi.org/10.1002/jps.2600720914

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elaini St, P.O. box 11562, Cairo, Egypt

    Noha Samy Mostafa, Ghada AbdElHamid, Hala Elsayed Zaazaa & Sawsan Mohamed Amer

Authors
  1. Noha Samy Mostafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ghada AbdElHamid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hala Elsayed Zaazaa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sawsan Mohamed Amer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noha Samy Mostafa.

Ethics declarations

Conflict of interest

All the authors working in this manuscript have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Samy Mostafa, N., AbdElHamid, G., Elsayed Zaazaa, H. et al. Two validated stability-indicating chromatographic methods for the separation of two anti-hypertensive combinations in the presence of their degradation products or impurities. Chem. Pap. 73, 2427–2439 (2019). https://doi.org/10.1007/s11696-019-00792-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11696-019-00792-z

Keywords

Search

Navigation