A sensitive column-switching HPLC method for aripiprazole and dehydroaripiprazole and its application to human pharmacokinetic studies.
A simple and sensitive column-switching HPLC-UV method was developed for the simultaneous determination of aripiprazole, a novel atypical antipsychotic drug, and its active metabolite, dehydroaripiprazole in human plasma. Aripiprazole, its active metabolite and 7-[5-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]pentyloxy]-3,4-dihydro-2(1H)-quinolinone (OPC-14558) as an internal standard were extracted from 1 mL of plasma using a mixture of chloroform/n-heptane (3:7, v/v), and the extract was injected into a column I (TSK BSA-ODS/S precolumn, 5 μm) for cleanup and column II (C(18) STR ODS-II analytical column, 5 μm) for separation. Peaks were detected with an UV detector set at a wavelength of 254 nm, and the total time for chromatographic separation was ∼20 min. Mean absolute recoveries were 74.0 and 74.7% for aripiprazole and dehydroaripiprazole, respectively. Intra- and inter-day CVs were less than 7.5 and 7.1% for aripiprazole concentrations ranging from 2 to 600 ng/mL, and 9.2 and 4.5% for dehydroaripiprazole concentrations ranging from 2 to 160 ng/mL. The validated concentration ranges for this method were 1-500 ng/mL and the limits of detection were 0.5 ng/mL for both aripiprazole and dehydroaripiprazole. This method was applied to pharmacokinetic study in human volunteers and patients taking aripiprazole.
Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Yumiko
Y
Akamine
Norio
N
Yasui-Furukori
Midori
M
Kojima
Yoshimasa
Y
Inoue
Tsukasa
T
Uno
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000068180:Aripiprazole; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010879:Piperazines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D015363:Quinolones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; C517414:dehydroaripiprazole; D000068180:Aripiprazole