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Current Chinese Chemistry

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ISSN (Print): 2666-0016
ISSN (Online): 2666-0008

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Research Article

Bioanalytical Method Development and Validation of Cilnidipine and Metoprolol Succinate by RP-HPLC: Its Pharmacokinetic Application

Author(s): Ramanlal N. Kachave* and Suvarna H. Shelke

Volume 2, Issue 1, 2022

Published on: 16 June, 2021

Article ID: e160621194113 Pages: 6

DOI: 10.2174/2210676611666210616142035

Price: $65

Abstract

Background: Cilnidipine and Metoprolol Succinate are antihypertensive agents used in the treatment of hypertension. Methods: A pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma was carried out using the chromatographic method.

Methods: The chromatographic method involved a reverse phase C18 column, using acetonitrile and pH 4.0 water in the ratio of 80:20 v/v as mobile phase, a flow rate of 1.2 ml/min, and UV detection at 231 nm. In-vivo pharmacokinetic studies were performed on rats. Rats were treated with Cilnidipine (1mg/kg) and Metoprolol Succinate (1 mg/kg) orally, and blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12 and 24 h post-treatment.

Results: The retention time of Plasma, Cilnidipine and Metoprolol Succinate was found to be 2.3, 3.1 and 5.5 min, respectively. Linearity was acceptable in the concentration range of 2-10 and 10- 50 for Cilnidipine and Metoprolol Succinate, respectively. The intra-day and inter-day variances were found to be less than 2. The mean recovery of Cilnidipine and Metoprolol Succinate was 100.12 and 100.15, respectively. The assay was successfully applied to a pharmacokinetic study in rat after oral administration. After oral administration, maximal concentration (Cmax) of Cilnidipine and Metoprolol Succinate was found to be 460.01 and 642.13 (μg g/mL), and the halflife was found at 2.0 and 3.904 hours, respectively.

Conclusion: The present method was successfully applied to the pharmacokinetic study of Cilnidipine and Metoprolol Succinate in rat plasma after oral administration.

Keywords: Cilnidipine, metoprolol succinate, RP-HPLC, pharmacokinetic study, rat plasma, validation of cilnidipine.

Graphical Abstract

[1]
Valic, M.S.; Halim, M.; Schimmer, P.; Zheng, G. Guidelines for the experimental design of pharmacokinetic studies with nanomaterials in preclinical animal models. J. Control. Release, 2020, 323, 83-101.
[http://dx.doi.org/10.1016/j.jconrel.2020.04.002] [PMID: 32278829]
[2]
Sica, D.A. Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs, 2002, 62(3), 443-462.
[http://dx.doi.org/10.2165/00003495-200262030-00003] [PMID: 11827559]
[3]
The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, Merck Reasearch Laboratories; 2006, 493, p. 6149.
[4]
Shinji, T.; Denan, J.; Shizuka, A.; Kazumi, N.; Mizuo, M. Powerful vascular protection by combining cilnidipine with valsartan in stroke-prone, spontaneously hypertensive rats. Hypertens. Res., 2013, 36, 342-348.
[http://dx.doi.org/10.1038/hr.2012.187]
[5]
Brunton, L.L.; Hilal-Dandan, R.; Knollmann, B.C. Goodman, and Gilman’s The pharmacology basis of therapeutics. Medical publishing Division: New York, 2001, pp. 249-260.
[6]
British pharmacopoeia, Vol. I and II, 2009, pp. 3933-3042.
[7]
United State Pharmacopoeia 30- National Formulary, 2007, 3(25), Asian edition, United State Pharmacopoeial Convention, Inc; 2647.
[8]
Kario, K.; Nariyama, J.; Kido, H.; Ando, S.; Takiuchi, S.; Eguchi, K.; Niijima, Y.; Ando, T.; Noda, M. Effect of a novel calcium channel blocker on abnormal nocturnal blood pressure in hypertensive patients. J. Clin. Hypertens. (Greenwich), 2013, 15(7), 465-472.
[http://dx.doi.org/10.1111/jch.12113] [PMID: 23815534]
[9]
Minami, J.; Ishimitsu, T.; Kawano, Y.; Numabe, A.; Matsuoka, H. Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard. J. Cardiovasc. Pharmacol., 1998, 32(2), 331-336.
[http://dx.doi.org/10.1097/00005344-199808000-00023] [PMID: 9700998]
[10]
Lee, H.W.; Seo, J.H.; Lee, H.S.; Jeong, S.Y.; Cho, Y.W.; Lee, K.T. Development of a liquid chromatography/negative-ion electrospray tandem mass spectrometry assay for the determination of cilnidipine in human plasma and its application to a bioequivalence study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2008, 862(1-2), 246-251.
[http://dx.doi.org/10.1016/j.jchromb.2007.11.016] [PMID: 18155975]
[11]
Xianhua, Z.; Suodi, Z.; Rongsheng, Z.; Jin, O.; Li, X.; Willy, R.G. Baeyens, Determination of cilnidipine, a new calcium antagonist, in human plasma using high performance liquid Chromatography with tandem mass spectrometric detection. Analytica chemica acta, 2007, 600, 142-146.
[http://dx.doi.org/10.1016/j.aca.2006.11.072]
[12]
Pawar, P.; Gandhi, S.V.; Deshpande, P.B.; Vanjari, S.; Shelar, S.U. Simultaneous RP-HPLC estimation of cilnidipine and telmisartan in combined tablet dosage form. Pelagia Research Library Der Chemica Sinica, 2013, 4(2), 6-10.
[13]
Minami, J.; Kawano, Y.; Makino, Y.; Matsuoka, H.; Takishita, S. Effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension. Br. J. Clin. Pharmacol., 2000, 50(6), 615-620.
[http://dx.doi.org/10.1046/j.1365-2125.2000.00299.x] [PMID: 11136301]
[14]
Aqil, M.; Ali, A.; Ahad, M.; Sultana, Y.; Najmi, A.K. Validated HPLC method for estimation of Metoprolol in Human plasma. Acta Chromatogr., 2007, 19, 130-140.
[15]
Prasada Rao, CHMM; Rahaman, SA; Ragjendra Prasad, Y Gangi Reddy, P RP-HPLC method of simultaneous estimation of Amlodipine Besylate and metoprolol in combined dosage form. International journal of pharmaceutical research and development, 2010, 2(9), 69-76.
[16]
Gosai, M.; Tanna, R.; Thumar, K.; Chikhalia, J. RP-HPLC method for simultaneous estimation of Metoprolol succinate and Clopidogrel bisulphate from tablet dosage. Inventi Rapid: Pharm Analysis &. Qual. Assur., 2012, 3, 1-7.
[17]
Chandra Bose, R.J.; Sivanseya, G. Krishna kumar, D. Validated RP-HPLC method for the simultaneous estimation of ramipril and metoprolol tartrate in bulk and tablet dosage form. Asian J. Biochem. Pharm. Res., 2011, 1(2), 171-177.
[18]
Bhargavi Durga, K; Naga Mounika, I; Shajhan, SK Srinivasa rao, N; Sarath, Chandra RP- HPLC method for estimation of Metaprolol in bulk drug. International journal of pharmaceutical research and development, 2012, 1(2), 151-157.
[19]
U.S. Department of Health and Human Services, Food and Drug Administration: In: Bioanalytical Method Validation, Guidance for Industry; 2013.

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