SPE–UPLC–MS/MS method for sensitive and rapid determination of aripiprazole in human plasma to support a bioequivalence study

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 925; pp. 20 - 25
• Main Authors: Patel, Daxesh P., Sharma, Primal, Sanyal, Mallika, Shrivastav, Pranav S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2013
• Subjects: Aripiprazole; Aripiprazole-d8; Bioequivalence; Chromatography; Chromatography, High Pressure Liquid - methods; Extraction; Formates; Human; Human plasma; Humans; Ionization; Linear Models; Linearity; Mathematical analysis; methanol; Methyl alcohol; monitoring; pharmacokinetics; Piperazines - blood; Piperazines - chemistry; Piperazines - pharmacokinetics; Quinolones - blood; Quinolones - chemistry; Quinolones - pharmacokinetics; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction - methods; Solid-phase extraction; storage conditions; Tandem Mass Spectrometry - methods; Therapeutic Equivalency; UPLC–MS/MS; Aripiprazole-d8; Human plasma; Bioequivalence; Aripiprazole; UPLC–MS/MS; Solid-phase extraction
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2013.02.022

► An improved UPLC–MS/MS method for determination of aripiprazole in human plasma. ► Highly sensitive and rapid compared to all existing methods in biological matrices. ► Practically free from endogenous matrix interference. ► Successful bioequivalence study in healthy Indian subjects. ► Reproducibility of study data is demonstrated by incurred sample reanalysis. An improved and rugged UPLC–MS/MS method has been developed and validated for sensitive and rapid determination of aripiprazole in human plasma using aripiprazole-d8 as the internal standard (IS). The analyte and IS were extracted from 100μL of human plasma by solid-phase extraction using Phenomenex Strata-X (30mg, 1cc) cartridges. Chromatography was achieved on an Acquity UPLC BEH C18 (50mm×2.1mm, 1.7μm) analytical column using methanol: 10mM ammonium formate (85:15, v/v) as the mobile phase with isocratic elution. Quantitation was done using multiple reaction monitoring in the positive ionization mode. The linearity of the method was established in the concentration range 0.05–80ng/mL. The mean extraction recovery was greater than 96% across QC levels, while intra- and inter batch accuracy and precision (% CV) values ranged from 97.4 to 101.9% and from 1.20 to 3.72% respectively. The relative matrix effect in eight different lots of plasma samples, expressed as % CV for the calculated slopes of calibration curves was 1.08%. The stability of aripiprazole was studied under different storage conditions. The validated method was used to support a bioequivalence study of 10mg aripiprazole formulation in 36 healthy Indian subjects.