A liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitation of aripiprazole in human plasma.
A rugged liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS-MS) method was developed and validated for accurate monitoring of steady-state plasma aripiprazole. Haloperidol-d(4) was chosen as the internal standard. ESI of aripiprazole and haloperidol-d(4) yielded abundant MH(+) ions, m/z 448 and 379, respectively. These ions were collision-dissociated to respective product ions of m/z 285 and 168. Ion-suppression experiments with blank plasma extracts showed substantial depressions of the product ions at retention times between 0.5 to 2 min, prohibiting development of a high-throughput LC-MS-MS method. A steep-gradient elution LC permitted a robust LC-ESI-MS-MS method with a 12-min analysis time. Aripiprazole was quantified from 0.2-mL aliquots of human plasma with acceptable precision and accuracy down to a lower limit of quantitation of 2 ng/mL. Aripiprazole was stable in plasma samples stored at room temperature for 24 h or exposed to three freeze-thaw cycles and in processed extracts stored at -20 degrees C for six days or on the autosampler at 10 degrees C for four days. The method has been successfully used for determinations of steady-state concentrations of aripiprazole in human subjects given daily oral doses of 15 mg. All measured concentrations were well within the quantitative range of 2 to 400 ng/mL.
Lin
Shen-Nan
SN
Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA. Shen-Nan.Lin@hsc.utah.edu
Lamm
Lolita
L
Newton
Thomas F
TF
Reid
Malcolm S
MS
Moody
David E
DE
Foltz
Rodger
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000494:pharmacology; D000068180:Aripiprazole; D002851:Chromatography, High Pressure Liquid; D006220:Haloperidol / Q000097:blood; D006801:Humans; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000494:pharmacology; D015363:Quinolones / Q000097:blood* / Q000494:pharmacology; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D006220:Haloperidol