Development and validation of a rapid and sensitive LC-MS/MS method for the determination of aripiprazole in human plasma: Application to a bioequivalence study

Abstract

Summary.A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of aripiprazole in human plasma. The analyte and propranolol as internal standard (IS) were extracted from 200 µL of human plasma via liquid-liquid extraction using methyl tert-butyl ether under alkaline conditions. The best chromatographic separation was achieved on an Aquasil C18 (100 × 2.1 mm, 5 µm) column using methanol-deionized water containing 2 mM ammonium trifluoroacetate and 0.02% formic acid (65:35, v/v) as the mobile phase under isocratic conditions. Detection of analyte and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The method was fully validated for its selectivity, interference check, sensitivity, carryover check, linearity, precision and accuracy, reinjection reproducibility, recovery, matrix effect, ion suppression/enhancement, stability, ruggedness, and dilution integrity. The assay was linear over the concentration range of 0.10-100 ng mL −1 for aripiprazole. The intra-batch and inter-batch precision (%CV) was ≤4.8%, while the mean extraction recovery was >96% for aripiprazole across quality control levels. The method was successfully applied to a bioequivalence study of 10 mg aripiprazole orally disintegrating tablet formulation in 27 healthy Indian subjects under fasting and fed condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 260 incurred samples.

Towards Precision Medicine in Clinical Practice: Alinity C vs. UHPLC-MS/MS in Plasma Aripiprazole Determination

“…In this sense, accurate quantification of aripiprazole is crucial for tailoring treatment strategies to individual patient needs, minimizing adverse effects and optimizing therapeutic efficacy [ 11 , 12 ]. Liquid chromatographic methods for the analysis of aripiprazole are widely described in the literature: there are LC-MS/MS [ 13 , 14 , 15 , 16 ], HPLC-UV/DAD [ 17 , 18 , 19 ] or GC-MS [ 20 ]-based methods.…”

Development and validation of zero and first-order derivative area under curve spectrophotometric methods for the determination of aripiprazole in bulk material and tablets

“…HPLC [3][4][5][6][7][8][9][10][11][12][13][14] in pharmaceutical formulation and biological fluid has been reported. Liquid chromatography coupled with mass spectrometry, [15][16][17][18][19][20][21][22][23] UPLC-MS 24,25 and few spectrophotometric methods. [26][27][28][29][30] However, till date no UV spectrophotometry method has been developed for the determination of ARP in bulk and pharmaceutical formulation using derivative spectroscopic techniques, AUC, and amplitude technique.…”