Determination of pirenzepine in human plasma using liquid chromatography with tandem mass spectrometric detection.
A sensitive (LOQ = 1 ng ml-1) and specific method based on liquid chromatography with tandem mass spectrometric (MS/MS) detection has been developed and validated for the analysis of pirenzepine (I) in plasma. Sample preparation involved liquid-liquid extraction of drug and internal standard (IS) from basified plasma. The organic extract was evaporated to dryness, and the residue was reconstituted in the mobile phase and then injected into the liquid chromatography/MS/MS system. Drug, IS, and endogenous impurities were separated using reverse-phase chromatography. A Sciex API III tandem mass spectrometer equipped with a heated nebulizer was operated in the positive ion mode. Multiple reaction monitoring using the parent-->daughter ion combinations of m/z 352-->113 and 629-->422 was used to quantify I and IS, respectively. The method was validated in the concentration range of 1-100 ng ml-1 plasma with adequate assay precision and accuracy, and was utilized to support human safety and tolerability study with I.
Chavez
C M
CM
Merck Research Laboratories, West Point, PA 19486, USA.
Constanzer
M L
ML
Matuszewski
B K
BK
D000897:Anti-Ulcer Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D018727:Muscarinic Antagonists / Q000097:blood*; D010890:Pirenzepine / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results
D000897:Anti-Ulcer Agents; D018727:Muscarinic Antagonists; D010890:Pirenzepine