Simultaneous determination of atorvastatin, amlodipine, ramipril and benazepril in human plasma by LC‐MS/MS and its application to a human pharmacokinetic study

Abstract

A rapid, simple, sensitive and specific LC-MS/MS method has been developed and validated for the simultaneous estimation of atorvastatin (ATO), amlodipine (AML), ramipril (RAM) and benazepril (BEN) using nevirapine as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Analytes and IS were extracted from plasma by simple liquid-liquid extraction technique using ethyl acetate. The reconstituted samples were chromatographed on C(18) column by pumping 0.1% formic acid-acetonitrile (15:85, v/v) at a flow rate of 1 mL/min. A detailed validation of the method was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 0.26-210 ng/mL for ATO; 0.05-20.5 ng/mL for AML; 0.25-208 ng/mL for RAM and 0.74-607 ng/mL for BEN with mean correlation coefficient of ≥0.99 for each analyte. The intra-day and inter-day precision and accuracy results were well with in the acceptable limits. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The developed assay method was successfully applied to a pharmacokinetic study in human male volunteers.

Quantitative Determination of Amlodipine Besylate, Losartan Potassium, Valsartan and Atorvastatin Calcium by HPLC in their Pharmaceutical Formulations

“…BP described a RP-HPLC method for assay of Amlodipine besylate and potentiometric titrations for assay of Atorvastatin calcium, Losartan potassium and Valsartan [3]. Several methods have been published for simultaneous determination of studied drugs in their combinations with each other, these methods depends on different analytical technique like Spectrophotometry [4][5][6][7][8][9][10][11], Spectrofluorimetry [12][13][14], Capillary Electrophoresis [15][16][17][18], HPTLC and TLC [19][20][21] and HPLC coupled with UV detector [21][22][23][24][25][26][27][28][29], fluorescence detector [30] and mass spectrometer detector [31][32][33][34]. Our scope is development of a validated analytical method for assay of these drugs in combination with each other in its pharmaceutical preparations and it should be characterized by a simplicity, accuracy, preciseness and sensitivity.…”

Simultaneous quantification of ramipril, glimepiride and metformin in human plasma by ultra-performance liquid chromatography – tandem mass spectrometry

“…Regarding the methods of analysis of the three drugs in biological fluids, several techniques were used for the quantification of RAM in the biological fluids including liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Gupta et al, 2011;Pilli et al, 2011;Patel et al, 2014), high performance liquid chromatography (HPLC) (Kurade et al, 2009) and spectrophotometry (Al-Majed et al, 2001). GLM was determined by LC-MS/MS methods either individually or with some other drugs in biological samples (Salem et al, 2004;Chakradhar et al, 2007;Liu et al, 2010).…”

Simultaneous Determination of Amlodipine and Atorvastatin in Caduetâ® Tablets Using HPLC

“…These methods include spectrophotometric (Darwish et al, 2011) and Chromatographic (Shariati et al, 2013;Pilli et al, 2011) methods.…”