Journal Article

A Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Quantitation of Aripiprazole in Human Plasma

Shen-Nan Lin, Lolita Lamm, Thomas F. Newton, Malcolm S. Reid, David E. Moody and Rodger L. Foltz

in Journal of Analytical Toxicology

Volume 33, issue 5, pages 237-242
Published in print June 2009 | ISSN: 0146-4760
Published online June 2009 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/33.5.237
A Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Quantitation of Aripiprazole in Human Plasma

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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-d4 was chosen as the internal standard. ESI of aripiprazole and haloperidol-d4 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°C for six days or on the autosampler at 10°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.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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