Determination of a specific 5-HT2a antagonist (M100907) in rat and dog plasma at the femtomole/milliliter level by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method for the determination of R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)-4-p iperdinemethanol] (M100907), I, in rat and dog plasma is described. I, a specific 5-HT2a receptor antagonist and the internal standard were concentrated from plasma by C1 solid-phase extraction. Following derivatization to their TMS ethers, they were separated by capillary GC and detection was by mass specific detection in single-ion monitoring mode. The validation range was from 0.1 to 10 ng/ml. The day-to-day coefficient of variation for the calibration standards over the concentration range varied from 9.5 to 14.9% in dog plasma and 1.7 to 13.4% in rat plasma. Quality control standards were measured at three concentrations (0.5, 2.5 and 7.5 ng/ml) in plasma from both species; the day-to-day coefficient of variation ranged from 1.8 to 14.2% in dog plasma and 1.6 to 15.1% in rat plasma. The method is both specific and sensitive down to the picomolar level in plasma.