SIMULTANEOUS ESTIMATION OF PROPAFENONE AND ITS TWO METABOLITES IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY LC-MS/MS


Rajeev Kumar Gupta, Anand Chaurasia, Brijeshkunvar Mishra

Abstract


Objective: A simple, sensitive and rapid performance liquid chromatography/positive ion electrospray tandem mass spectrometry method was to be developed and validated for quantification of propafenone (PPF) and its two major metabolite 5-hydroxy propafenone (5-OHP) and N-depropyl propafenone (NDP) in human plasma.

Methods: Liquid-liquid extraction (LLE) with ethyl acetate was used of extraction of plasma samples. The analytes were separated using an isocratic mixture of 0.1% formic acid/acetonitrile (20:80 v/v) on a reversed-phase column Hypurity Advance C18 50 x2.1 mm, 5µ and analysed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H] Ions. The m/z was 342.20/116.10 for propafenone, m/z 299.80/74.10 for N depropyl propafenone and m/z 358.30/98.10 for 5-hydroxy propfenone along with m/z 409.2/238.0 for Amlodipine as internal standard respectively.

Results: The method had a short chromatographic run time of 1.5 min. The method exhibited a linear dynamic range over 5.11 to 1000.73 ng/ml for propafenone, 0.51 to 100.06 ng/ml for N-depropyl propafenone and 5.11 to 1001.64 ng/ml for 5-hydroxy propafenone respectively, in human plasma.

Conclusion: The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetics, bioavailability and bioequivalence studies.


Keywords


Stability, N-depropyl propafenone, 5-hydroxy propafenone, Amlodipine, Validation, LC-MS

| PDF | HTML |

References


Reimold SC, Maisel WH, Antman EM. Propafenone for treatment fo supraventricular tachycardia and atrial fibrillation: a meta analysis. Am J Cardiol 1998;82:66-71.

Dollery C. Therapeutic drugs. 2nd ed. Edinburgh (UK): Churchill living stone; 1999.

Kates RE, Yee YG, Winkle RA. Metabolite cumulation during chronic propafenone dosing in arrhythmia. Clin Pharmacol Ther 1985;37:610-4.

Hege HG, Hollmann M, Kaumeier S, Lietz H. The metabolic fate of 2H-labeled propafenone in man. Eur J Drug Metab Pharmacokinet 1984;9:41-5.

Valenzuela C, Delgado C, Tamargo J. Electrophysiological effects of 5-hydroxy propafenone on guinea pig ventricular muscle fiber. J Cardiovasc Pharmacol 1987;10:523-9.

Zhong D, Chen X. Enantioselective determination of propafenone and its metabolites in human plasma by liquid chromatography–mass spectrometry. J Chromatogr B 1999;721:67-75.

Afshar M, Rouini M. A rapid HPLC assay for the simultaneous determination of propafenone and its major metabolites in human serum. Anal Sci 2004;20:1307-11

Hofmann U, Pecia M, Heinkele G, Dilger K, Kroemer HK, Ecihelbaum M. Determination of propafenone and its phase I and II metabolites in plasma and urine by high-performance liquid chromatography-electronspray ionization mass spectrometry. J Chromatogr B 2000;748:113-23.

Kubalec P, Bransteterova E. Determination of propafenone and its main metabolite 5-hydroxypropafenone in human serum with direct injection into a column-switching chromatographic system. J Chromatogr B 1999;726:211-8

L Pan, Y Qian, Cheng M, Gu P, He Y, Xu L, et al. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs. Acta Pharm Sin B 2015;5:74-8.

Sujan Kumar DP, Palavan C, Sheshagiri Rao JVLN. A rapid and sensitive LC-MS/MS assay for the determination of propafenone and its active metabolite 5-hydroxy propafenone in human plasma using SPE precipitation technology. Pharm Lett 2015;7:122-8.

Sharma D, Mittal R, Gupta A, Singh K, Nair A. Quantitative bioanalysis by LC-MS/MS: a review. J Pharm Biomed Sci 2010;7:1-9.




About this article

Title

SIMULTANEOUS ESTIMATION OF PROPAFENONE AND ITS TWO METABOLITES IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY LC-MS/MS

Keywords

Stability, N-depropyl propafenone, 5-hydroxy propafenone, Amlodipine, Validation, LC-MS

DOI

10.22159/ijpps.2017v9i8.18978

Date

01-08-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 8, 2017 Page: 192-199

Online ISSN

0975-1491

Statistics

57 Views | 85 Downloads

Authors & Affiliations

Rajeev Kumar Gupta
Department of Pharmaceutical Sciences, MJRP University, Jaipur
India

Anand Chaurasia
Department of Pharmacy, RKDF University, Bhopal
India

Brijeshkunvar Mishra
School of Pharmacy, RGPV, Bhopal
India


Article Tools



Refbacks

  • There are currently no refbacks.