Development and validation of a method for quantitative determination of valsartan in human plasma by liquid chromatography-tandem mass spectrometry.
A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of valsartan in human plasma was developed and validated. A 0.5 ml aliquot was extracted using solid-phase extraction in an Empore high performance extraction disk plate, universal resin 96-well format. The estimated calibration range of the method was 2-2000 ng/ml. The method was fully validated with intra-day mean accuracy and precision of 94.8-107% and 2.19-5.40% and inter-day mean accuracy and precision of 93.5-105% and 1.87-5.67%, respectively. No significant loss of valsartan in processed samples was confirmed in processed samples for up to 24 h at 10 degrees C. Sample dilution up to 50-fold with blank human plasma provided acceptable analyses. No interference peaks or matrix effects were observed. No effect of QC sample location results was observed in a 96-well plate. This LC-MS/MS technique was found to improve quantitative determination of valsartan allowing its pharmacokinetic evaluation with clinically relevant doses.
Koseki
Nozomu
N
Drug Metabolism and Pharmacokinetics, Tsukuba Research Institute, Novartis Pharma K.K., Ohkubo 8, Tsukuba-shi, Ibaraki 300-2611, Japan. nozomu.koseki@novartis.com
Kawashita
Hiroto
H
Hara
Hisanori
H
Niina
Miyuki
M
Tanaka
Makoto
M
Kawai
Ryosei
R
Nagae
Yusuke
Y
Masuda
Naoki
N
D000959:Antihypertensive Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D013777:Tetrazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D014633:Valine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine