Quantifcation of atorvastatin in human plasma by liquid chromatography tandem mass spectrometry and its application for bioequivalence study of three formulations

Yahdiana Harahap,Santi Purnasari,Harmita,Rina Rahmawati, Krisnasari Dian,Pratami,Witri Sansris,Siti Fatriyah

Laboratory of Bioavailability and Bioequivalence,Faculty of Pharmacy Universitas Indonesia,Depok 16424, Indonesia

Quantifcation of atorvastatin in human plasma by liquid chromatography tandem mass spectrometry and its application for bioequivalence study of three formulations

Yahdiana Harahap*,Santi Purnasari,Harmita,Rina Rahmawati, Krisnasari Dian,Pratami,Witri Sansris,Siti Fatriyah

Laboratory of Bioavailability and Bioequivalence,Faculty of Pharmacy Universitas Indonesia,Depok 16424, Indonesia

A R T I C L E I N F O

Article history:

Available online 23 November 2015

Atorvastatin

Simvastatin

LC-MS/MS

Atorvastatin,a chemical([R-(R*,R*)]-2-(4-fuorophenyl)-b,ddihydroxy-5-(1-methylethyl)-3-phenyl-4-

[(phenylamino)carbonyl]1 H-pyrole-1-heptanoic acid),is a synthetic HMG-CoA(3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor.It has been shown to be remarkably effcacious in decreasing the level of cholesterol and triglyceride [1].In order to quantify the level of atorvastatin in plasma,it needs a sensitive,rapid and selective method.As per the literature,several LC–MS/MS methods have been reported for the determination of atorvastatin in human plasma[2].

This research developed a method to quantify atorvastatin in human plasma.Simvastatin was used as internal standard.Atorvastatin and simvastatin were extracted by liquid–liquid extraction using ethyl acetate.The analytical separation was performed using Acquity?UPLC BEH C18,100×2.1 mm, 1.7 μm.The mobile phase used gradient elution of 0.2%formic acid in acetonitrile,with fow rate of 0.3 mL/min.The analysis was carried out by multiple reaction monitoring(MRM)in positive mode using precursor to product combination of m/z 559.05>440 for atorvastatin and m/z 419.15>199.05 for simvastatin.The method had a chromatographic run time of 5 minutes and linear calibration curve over the range of 0.2–100 ng/mL with a correlation coeffcient(r)of 0.9998.All the validation parameters fulflled the criteria[3]and the method can be successfully applied for pilot bioequivalence studies of three formulations of atorvastatin.

R E F E R E N C E S

[1]Bakker-Arkema RG,Davidson MH,Goldstein RJ,et al.Effcacy and safety of a new HMG-CoA reductase inhibitor,atorvastatin,in patients with hypertriglyceridemia.J Am Med Assoc 1996;275:128–133.

[2]Macwan JS,Ionita IA,Dostalek M,et al.Development and validation of a sensitive simple and rapid method for simultaneous quantitation of atorvastatin and its acid and lactone metabolites by liquid chromatography-tandem mass spectrometry LC-MS/MS.Anal Bioanal Chem 2011;400:423–433.

[3]European Medicines Agency(EMA)Committee for Medicinal Products for Human Use.Guideline on bioanalytical method validation.Reff:EMEA/CHMP/EWP/192217/2009.London: European Medicines Agency;2011.

*E-mail address:yahdiana03@yahoo.com.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.048

1818-0876/?2016 The Authors.Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).