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.
Emmons
G T
GT
Hoechst Marion Roussel, Inc., Kansas City, MO 64134-0627, USA.
Danison
T H
TH
Steele
D
D
Sproles
G D
GD
D000818:Animals; D004285:Dogs; D004355:Drug Stability; D005464:Fluorobenzenes / Q000097:blood* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D008832:Microchemistry; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control; D051381:Rats; D012702:Serotonin Antagonists / Q000097:blood*; D012996:Solutions
D005464:Fluorobenzenes; D010880:Piperidines; D012702:Serotonin Antagonists; D012996:Solutions; C079049:volinanserin