An improved LC-MS/MS method for quantitative determination of metolazone in human plasma and its application to a pharmacokinetic study

A simple, rapid and accurate liquid chromatography-tandem mass spectrometry method has been developed. After a liquid-liquid extraction procedure, samples were chromatographed on an Agilent TC-C(18) (150 x 4.6 mm, 5 mu m) column using an isocratic elution mobile phase composed of methanol and distilled water (70: 30, v/v) at a flow rate of 0.5 mL/min. After single-dose administration of 0.5, 1 and 2 mg metolazone, the t(1/2) values were 6.6 +/- 2.8, 7.9 +/- 1.2 and 7.6 +/- 1.9 h, respectively. The pharmacokinetic parameters of multiple doses (1 mg metolazone) were as follows: t(1/2) was 8.9 +/- 1.0 h; C(max) was 22.4 +/- 5.0 ng/mL; and AUC(0-48) was 156.8 +/- 31.6 ng h/mL. Copyright (C) 2011 John Wiley & Sons, Ltd.