Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.
A simple and sensitive LC-MS method was developed and validated for the simultaneous quantification of aripiprazole (ARI), atomoxetine (ATO), duloxetine (DUL), clozapine (CLO), olanzapine (OLA), sertindole (STN), venlafaxine (VEN) and their active metabolites dehydroaripiprazole (DARI), norclozapine (NCLO), dehydrosertindole (DSTN) and O-desmethylvenlafaxine (OVEN) in human plasma. The above mentioned compounds and the internal standard (remoxipride) were extracted from 0.5 mL plasma by solid-phase extraction (mix mode support). The analytical separation was carried out on a reverse phase liquid chromatography at basic pH (pH 8.1) in gradient mode. All analytes were monitored by MS detection in the single ion monitoring mode and the method was validated covering the corresponding therapeutic range: 2-200 ng/mL for DUL, OLA, and STN, 4-200 ng/mL for DSTN, 5-1000 ng/mL for ARI, DARI and finally 2-1000 ng/mL for ATO, CLO, NCLO, VEN, OVEN. For all investigated compounds, good performance in terms of recoveries, selectivity, stability, repeatability, intermediate precision, trueness and accuracy, was obtained. Real patient plasma samples were then successfully analysed.
Choong
Eva
E
Unit of Biochemistry and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly-Lausanne, Switzerland.
Rudaz
Serge
S
Kottelat
Astrid
A
Guillarme
Davy
D
Veuthey
Jean-Luc
JL
Eap
Chin B
CB
D000928:Antidepressive Agents / Q000097:blood / Q000378:metabolism; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000295:instrumentation* / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry / Q000379:methods*; D011619:Psychotropic Drugs / Q000097:blood* / Q000378:metabolism*; D012016:Reference Values; D015203:Reproducibility of Results; D013048:Specimen Handling; D013696:Temperature; D013997:Time Factors
D000928:Antidepressive Agents; D011619:Psychotropic Drugs