4 mL/min. The samples were kept at 4 °C in an autosampler, and a volume of 10 μL was injected for analysis. Mass spectrometric detection was performed on a 3200 QTrap® instrument (ABI-Sciex, Toronto, ON, Canada) equipped with a turbo spray interface and operated in positive ionization mode. The dwell time was set at 200 ms,

BIX 1294 clinical trial and the ion source temperature was set at 450 °C, with ultra-high-purity nitrogen as the curtain gas (20) and collision gas (medium). The ion spray voltage was set at 1,900 V. Multiple reaction monitoring transitions were at mass-to-charge ratios (m/z) of 411.3 → 191.3 and 415.3 → 195.3 for risperidone and d4-risperidone, respectively, and 427.2 → 207.2 and 431.2 → 211.2 for 9-hydroxy-risperidone and d4-9-hydroxy-risperidone, respectively. Data acquisition and processing were powered by the Analyst® 1.4.2 software package (Applied Biosystems, Foster City, CA, USA). The methods were linear from 0.1 to 50 ng/mL for both risperidone and the active metabolite, 9-hydroxy-risperidone. The lower limit of quantification was established at 0.1 ng/mL for both analytes. Quality control samples (0.1, 0.25, 25, 40 ng/mL) for both analytes within the calibration

range were routinely analyzed with study samples. Intra-day assay validation indicated precision of 0.8–9.4% and accuracy of 92.8–104.0% for the quality control samples of risperidone, and the inter-day precision ranged from 1.5% to 7.6%, with accuracy of 97.2–104.0%. For 9-hydroxy-risperidone, the intra-day precision ranged from 1.1% to 9.1%, with accuracy of 93.8–103.8%, and the inter-day FHPI mouse precision ranged from 1.4% to 6.1%, with accuracy of 96.9–100.8%. Both risperidone and 9-hydroxy-risperidone were stable in human plasma Mocetinostat following three freeze–thaw Farnesyltransferase cycles, for 24 hours at room temperature, for up to 4 weeks following storage at −30 °C, and for 24 hours after being processed. The coefficients of variation for stability tests were all within 20%, which met the acceptance criteria of our laboratory’s standard operating procedure. The stability tests that were performed indicated that

there was no significant degradation under the conditions that were described. 2.5 Pharmacokinetic and Statistical Analysis Pharmacokinetic analysis was conducted with a noncompartmental method, using Drug and Statistics (DAS) software version 2.0 (University of Science and Technology, Hefie, China). The Cmax and the time to reach the Cmax (tmax) were obtained directly from the concentration–time curves. Pharmacokinetic properties were analyzed by noncompartmental pharmacokinetic data analysis using PKCalc software (1986 release), based on an equation described by Shumaker [18]. The area under the plasma concentration–time curve (AUC) from time zero to time t (AUCt) was calculated according to the linear trapezoidal rule.