An improved simple LC-MS/MS method for the measurement of serum aripiprazole and its major metabolite

J Pharm Biomed Anal. 2012 Mar 25:62:135-9. doi: 10.1016/j.jpba.2012.01.003. Epub 2012 Jan 14.

Abstract

Background and objectives: Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection.

Method: We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection.

Results: Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 ± 4.5% for Ar and 97.6 ± 7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs.

Conclusion: Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods.

Publication types

  • Validation Study

MeSH terms

  • Antipsychotic Agents / blood*
  • Aripiprazole
  • Calibration
  • Chromatography, Liquid / methods*
  • Humans
  • Limit of Detection
  • Piperazines / blood*
  • Quinolones / blood*
  • Reference Standards
  • Reproducibility of Results
  • Solid Phase Extraction
  • Tandem Mass Spectrometry / methods*

Substances

  • Antipsychotic Agents
  • Piperazines
  • Quinolones
  • Aripiprazole