Determination of an arylether antiarrhythmic and its N-dealkyl metabolite in rat plasma and hepatic microsomal incubates using liquid chromatography-tandem mass spectrometry.
A method was developed and validated for the quantification of (+/-)-trans-[2-morpholino-1-(1-naphthalene-ethyloxy]cyclohexane monohydrochloride (RSD1070) and its N-dealkyl metabolite in rat plasma and hepatic microsomal incubates. Chromatographic separations were achieved using reversed-phase high-performance liquid chromatography coupled with positive ion electrospray ionization and detection by tandem mass spectrometry. The assay was linear from 2.5 to 100 ng/ml and this range was used for validation. Inter- and intra-assay variability (n=6), extraction recovery, and stability in plasma were assessed. The estimated limit of quantitation was in the range 2.5-3 ng/ml for both analytes in rat plasma. The analytical method was used in a pharmacokinetic study of RSD1070 in rats after a single i.v. bolus of 12 mg/kg.
Tong
V
V
Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Sheng
T
T
Walker
M J
MJ
Abbott
F S
FS
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009025:Morpholines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000889:Anti-Arrhythmia Agents; D009025:Morpholines; D009281:Naphthalenes; C433371:RSD1070