Determination of ZD9583, a thromboxane receptor antagonist, in human plasma and urine by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry |
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Authors: | Chun Xin Gao Khanh H Bui Angela S Martz Norman C LeDonne Martin C Dyroff |
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Institution: | Drug Disposition and Metabolism Department, Zeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19850,USA |
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Abstract: | A liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry (LC–APCI-MS–MS) method is described for the determination of a thromboxane receptor antagonist (4Z)-6-((2S,4S,5R)-2-(1-(2-cyano-4-methylphenoxy)-1-methylethyl)-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 C8 reversed-phase chromatography column. Following the diversion of the solvent front from the mass spectrometer by a switching valve, the column eluate is passed on to the mass spectrometer via a heated nebulizer interface 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- and inter-day precision estimates of less than 10% over the calibration range. |
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Keywords: | Thromboxane receptor antagonist ZD9583 |
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