LC-MS Method for Determining Amiodarone and Desethylaminodarone in Rat Plasma Used in Endogenous Overdosing Conditions Following Lipolysis

Open access

Abstract

Objective: The purpose of this study was to develop a LC-MS method to determine amiodarone (AMI) and its major metabolite desethylamiodarone (DEA) from rat plasma released from the adipose tissue of AMI treated rats subjected to a weight gain/weight loss cycle. Methods: Separation of the compounds was performed on a Kinetex 2.6 μm C18 100 x 4.6 mm column under isocratic conditions using a mixture of acetonitrile: 0.1% formic acid 65:35 at a flow rate of 0.5 ml/min. Detection of the analyte was performed by electrospray positive ionization, the monitored ions being 135 m/z from 646 for AMI and 135 m/z of 618 for DEA. Analytes were extracted after plasma protein precipitation with methanol. Results: The developed method presented specificity and linearity on the concentration range of 25-2500 ng/ml plasma for AMI and 2.5-1250 ng/ml plasma for DEA and the precision and accuracy of the method at all of quality control concentration levels including LLOQ were according to official guidelines for validating analytical methods. Conclusions: A sensitive and accurate LC-MS method has been developed with a much lower LLOQ than literature data to detect the plasma concentration differences of the studied analytes that result from forced lipolysis and mobilization from the adipose tissue.

1. Schleifer JW, Sorajja D, Shen WK - Advances in the pharmacologic treatment of ventricular arrhythmias. Expert Opin Pharmacother. 2015;16(17):2637-51.

2. Lu JT, Cai Y, Chen F, Jia WW, Hu ZY, Zhao YS - A Physiologically Based Pharmacokinetic Model of Amiodarone and its Metabolite Desethylamiodarone in Rats: Pooled Analysis of Published Data. Eur J Drug Metab Pharmacokinet. 2016 Dec;41(6):689-703.

3. Roden AC, Camus P - Iatrogenic pulmonary lesions. Semin Diagn Pathol. 2018 Jul;35(4):260-271.

4. Schumacher JD, Guo GL - Mechanistic review of drug-induced steatohepatitis. Toxicol Appl Pharmacol. 2015 Nov 15;289(1):40-7.

5. Santangeli P, Di Biase L, Burkhardt JD, Bai R, Mohanty P, Pump A, Natale A - Examining the safety of amiodarone. Expert Opin Drug Saf. 2012 Mar;11(2):191-214.

6. Lafuente-Lafuente C, Alvarez JC, Leenhardt A, Mouly S, Extramiana F, Caulin C, Funck-Brentano C, Bergmann JF - Amiodarone concentrations in plasma and fat tissue during chronic treatment and related toxicity. Br J Clin Pharmacol. 2009 May;67(5):511-9.

7. Shayeganpour A, Somayaji V, Brocks DR - A liquid chromatographymass spectrometry assay method for simultaneous determination of amiodarone and desethylamiodarone in rat specimens. Biomed Chromatogr. 2007 Mar; 21(3):284-90.

8. Najjar TA - Disposition of amiodarone in rats after single and multiple intraperitoneal doses.Eur J Drug Metab Pharmacokinet. 2001 Jan- Jun;26(1-2):65-9.

9. Binkhathlan Z, Somayaji V, Brocks DR, Lavasanifar A - Development of a liquid chromatography-mass spectrometry (LC/MS) assay method for the quantification of PSC 833 (Valspodar) in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 15;869(1-2):31-7.

10. Elsherbiny ME, El-Kadi AO, Brocks DR - The effect of betanaphthoflavone on the metabolism of amiodarone by hepatic and extrahepatic microsomes. Toxicol Lett. 2010 Jun 2;195(2-3):147-54.

11. Najjar TA - Disposition of amiodarone in rats after single and multiple intraperitoneal doses. Eur J Drug Metab Pharmacokinet. 2001 Jan- Jun;26(1-2):65-9.

12. Pathak RK, Mahajan R, Lau DH, Sanders P - The implications of obesity for cardiac arrhythmia mechanisms and management. Can J Cardiol. 2015 Feb;31(2):203-10.

13. Haley MJ, Mullard G, Hollywood KA, Cooper GJ, Dunn WB, Lawrence CB - Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice. Disease Models & Mechanisms. 2017;10(10):1229-1243.

Acta Medica Marisiensis

The Journal of The University of Medicine and Pharmacy of Targu-Mures

Journal Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 26 26 24
PDF Downloads 17 17 14