Enantioselective determination of mianserin and its desmethyl metabolite in plasma during treatment of depressed Japanese patients.
A method for the analysis of the enantiomers of mianserin and its main metabolite desmethylmianserin in plasma using a chiral AGP high performance liquid chromatography column is described. In the majority of 66 depressed Japanese patients, the concentration of the more active S(+)-mianserin was higher than that of the R(-)-enantiomer. The mean S/R ratio was 1.9 +/- 0.9 (SD) (range 0.5-4.8). The concentration of S(+)-varied between 19 and 223 nM, while that of the R(-)-mianserin varied between 14 and 72 nM. Among 42 of the 66 plasma samples in which the enantiomers of desmethylmianserin could be measured, the R-form predominated in all but one. S-Desmethylmianserin was in most of the samples present in concentrations of < 10 nM (limit of detection). Analysis of the enantiomers of mianserin and desmethylmianserin might allow the establishment of a closer relationship between plasma levels and clinical effects.
Tybring
G
G
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge Hospital, Sweden.
Otani
K
K
Kaneko
S
S
Mihara
K
K
Fukushima
Y
Y
Bertilsson
L
L
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D008875:Middle Aged; D013237:Stereoisomerism
D018687:Antidepressive Agents, Second-Generation; D008803:Mianserin; C056517:desmethylmianserin