Quantification of chlorprothixene, levomepromazine and promethazine in human serum using high-performance liquid chromatography with coulometric electrochemical detection.
Isocratic reversed-phase high-performance liquid chromatography with coulometric electrochemical detection was optimised to quantify the neuroleptic drugs chloroprothixene, levomepromazine, and promethazine in human serum. The method involves extraction of the neuroleptic drugs in n-heptane-isoamylalcohol from the alkalinized serum, followed by chromatographic separation on a Nucleosil CN column with acetonitrile-pyridine-sodium acetate buffer as the mobile phase. The extraction recovery was > 85% for each neuroleptic drug. The sensitivity and selectivity required for pharmacokinetic studies was obtained with a dual coulometric analytical cell operating in the oxidative screen mode. The lower limit of detection in human serum for chlorprothixene, levomepromazine, and promethazine, was 0.5, 0.2 and 0.1 ng/ml, respectively. A linear relationship (r2 > 0.99) was obtained between the concentrations of each neuroleptic drug and the detector signal. The accuracy of the quality control samples was +/- 7% for each neuroleptic drug with a precision within 9.5%, 8.1% and 13.5% for chlorprothixene, levomepromazine, and promethazine, respectively. The neuroleptic drugs were stable in acetonitrile and human serum for at least six months when stored at -20 degrees C. This method is applicable to analyze a large number of serum samples for pharmacokinetic studies of the neuroleptic drugs.
Bagli
M
M
Psychiatrische Klinik und Poliklinik, Rheinischen Friedrich-Wilhelms Universität, Bonn, Germany.
Rao
M L
ML
Höflich
G
G
D002749:Chlorprothixene / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004355:Drug Stability; D004563:Electrochemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D008728:Methotrimeprazine / Q000097:blood* / Q000493:pharmacokinetics; D011398:Promethazine / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control
D008728:Methotrimeprazine; D002749:Chlorprothixene; D011398:Promethazine