DETERMINATION OF ZD9583, A THROMBOXANE RECEPTOR ANTAGONIST, IN HUMAN PLASMA AND URINE BY LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION TANDEM MASS-SPECTROMETRY

A liquid chromatography-atmospheric pressure chemical ionization tande m mass spectrometry (LC-APCI-MS-MS) method is described for the determ ination of a thromboxane receptor antagonist thylethyl)-4-(3-pyridyl)- 3-dioxan-5-yl)hex-4-enoic acid (ZD9583, I) in human plasma and urine. Proteins in plasma and urine samples are precipitated using acidified acetonitrile. The resulting supernatant is chromatographed on a C-8 re versed-phase chromatography column. Following the diversion of the sol vent front from the mass spectrometer by a switching valve, the column eluate is passed on to the mass spectrometer via a heated nebulizer i nterface where the analyte is detected by multiple reaction monitoring (MRM). The method has a chromatographic run time of less than 2 min, a linear calibration curve with a range of 1-500 ng ml(-1) and intra-a nd inter-day precision estimates of less than 10% over the calibration range. (C) 1997 Elsevier Science B.V.