Development and validation of a highly sensitive and robust LC‐ESI‐MS/MS method for simultaneous quantitation of simvastatin acid, amlodipine and valsartan in human plasma: application to a clinical pharmacokinetic study

Abstract

A high-throughput, simple, highly sensitive and specific LC-MS/MS method has been developed for simultaneous estimation of simvastatin acid (SA), amlodipine (AD) and valsartan (VS) with 500 microL of human plasma using deuterated simvastatin acid as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using electrospray ionization. The assay procedure involved precipitation of SA, AD, VS and IS from plasma with acetonitrile. The total run time was 2.8 min and the elution of SA, AD, VS and IS occurred at 1.81, 1.12, 1.14 and 1.81 min, respectively; this was achieved with a mobile phase consisting of 0.02 M ammonium formate (pH 4.5):acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-Terra C18 column. A linear response function was established for the range of concentrations 0.5-50 ng/mL (r > 0.994) for VS and 0.2-50 ng/mL (r > 0.996) for SA and AD. The method validation parameters for all three analytes met the acceptance as per FDA guidelines. This novel method has been applied to human pharmacokinetic study.

Development and Validation of HPLC Method for Simultaneous Determination of Amlodipine, Valsartan, Hydrochlorothiazide in Dosage Form and Spiked Human Plasma

“…However, there is very few analytical methods reported for the simultaneous analysis of these drugs in a combined dosage formulation [3,4]. The reported methods are UV spectrophotometric [5][6][7][8][9], Spectrofluorimetric [10] HPLC [11][12][13][14][15][16][17][18][19][20][21][22][23][24], HPTLC [25,26], capillary electrophoresis [27][28][29][30] and electrochemical [31][32][33][34] methods.…”

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.…”

Densitometry, video-scanning and capillary electrophoresis for determination of valsartan and amlodipine in a combined dosage form: A comparative study

“…Some of them include determination of the drugs in the presence of their degradation products [4,5]. Also, some LC-MS methods have been developed and applied to pharmacokinetic and toxicological studies [6,7]. On the other hand, there are only two papers concerning TLC analysis of these drugs in pharmaceutical combinations.…”