To establish and validate a highly sensitive and selective high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of lurasidone, which was used subsequently to clinical lurasidone blood drug concentration monitoring.

Tadalafil was used as internal standard. Following a deproteinization procedure, lurasidone and the internal standard (tadalafil) were isostatically eluted using a mobile phase composed of methanol and 0.1% aqueous formic acid (50：50, v/v) at a flow rate of 0.70 mL·min^-1. The chromatographic separation was achieved within 4.0 min on an Agilent ZORBAX Eclipse plus C₈(4.6 mm×100.0 mm，3.5 μm). Quantification was performed using a triple-quadrupole mass spectrometer operating in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM). The method was validated for selectivity, linearity (calibration curve), precision and accuracy, matrix effect, extraction recovesise, stability and dilutive integrity. The concentrations of 14 clinical samples were measured after this method was validated.

The calibration curve for lurasidone in human plasma demonstrated linearity over the concentration range of 0.50-500.00 ng·mL^-1. The precision data (both intra- and inter-day) for the three QC levels ranged from 2.87% to 10.03%. Accuracy (relative error) was within±15% of the nominal values. The plasma samples maintained stability for 28 h at room temperature, for 85 days at -20 ℃ and through five freeze-thaw cycles. The measured concentrations of clinical samples were within the range of the standard curve, with concentrations ranging from 2.63 to 21.17 ng·mL^-1.

The validated method is proved to be convenient, accurate, and sensitive for the quantification of lurasidone in human plasma. The method is proved to be suitable for the monitoring of plasma concentration and pharmacokinetics study of lurasidone.