Development and validation of a method for quantitative determination of valsartan in human plasma by liquid chromatography-tandem mass spectrometry

• Published in: Journal of pharmaceutical and biomedical analysis 2007-04, Vol.43 (5), p.1769-1774
• Main Authors: Koseki, Nozomu, Kawashita, Hiroto, Hara, Hisanori, Niina, Miyuki, Tanaka, Makoto, Kawai, Ryosei, Nagae, Yusuke, Masuda, Naoki
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antihypertensive Agents - blood; Antihypertensive Agents - chemistry; Antihypertensive Agents - pharmacokinetics; Biological and medical sciences; Chromatography, Liquid - methods; Drug Stability; Fundamental and applied biological sciences. Psychology; General pharmacology; Human pharmacokinetics; Humans; Inter-subject variability; Liquid chromatography-tandem mass spectrometry; Matrix effects; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; Temperature; Tetrazoles - blood; Tetrazoles - chemistry; Tetrazoles - pharmacokinetics; Valine - analogs & derivatives; Valine - blood; Valine - chemistry; Valine - pharmacokinetics; Valsartan
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2006.12.030

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 °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.