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 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.
Gao
C X
CX
Drug Disposition and Metabolism Department, Zeneca Pharmaceuticals, Wilmington, DE 19850, USA.
Bui
K H
KH
Martz
A S
AS
LeDonne
N C
NC
Dyroff
M C
MC
D001274:Atmospheric Pressure; D002853:Chromatography, Liquid; D004355:Drug Stability; D006461:Hemolysis; D006801:Humans; D013058:Mass Spectrometry; D011725:Pyridines / Q000097:blood* / Q000652:urine*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D011725:Pyridines; D017482:Receptors, Thromboxane; C105662:ZD 9583