Multiquant version 2

Data acquisition and LC-MS/MS operation were conducted using Analyst® TF Version 1.6 (Sciex, Redwood City, CA, USA). MultiQuant® Version 2.1.1 (Sciex, Redwood City, CA, USA) was used for peak integration for MMAF quantification. The descriptive statistics for the qualification studies were calculated with Excel 2015 (Microsoft, Seoul, Korea). Pharmacokinetic parameters were calculated in a non-compartmental analysis using WinNonlin® version 8.0.0 (Certara, Princeton, NJ, USA). PeakView® Version 2.2 (Sciex, Redwood City, CA, USA) and MetabolitePilot^TM Version 2.0.2 (Sciex, Redwood City, CA, USA) were used for the structural elucidation of metabolites. MedChem Designer (Simulations Plus, Inc, Lancaster, CA, USA) was used for in silico metabolite prediction.

Data acquisition and LC–QTOF-MS operation was conducted using Analyst^® TF Version 1.6 (Sciex). MultiQuant^® Version 2.1.1 (Sciex) was used for the peak integration of omeprazole for quantification. PeakView^® Version 2.2 and MetabolitePilot^TM Version 2.0.2 were used for the structural elucidation of omeprazole metabolites. Pharmacokinetic parameters were calculated in a non-compartmental analysis using WinNonlin^® version 8.0.0 (Certara, Princeton, NJ, USA).

Analyst^® TF Version 1.6 (Sciex, Foster City, CA, USA) operated with Windows^® (Microsoft Corp., Redmond, WA, USA) was used for the instrument control as well as the data acquisition. MultiQuant^® Version 2.1.1 (Sciex, Foster City, CA, USA) was used for the peak integration. Excel 2015 (Microsoft) was used for all calculations including peak area ratios, standard curve regressions, sample concentration values, and descriptive statistics.

The plasma and brain PK parameters (terminal half-life (T_1/2), time to reach maximum concentration (T_max), the area under the curve up to the last time point (AUC_last)) were estimated from the mean concentrations at each time by non-compartmental analysis (NCA) using Phoenix WinNonlin^® Version 8.0.0 (Certara, Princeton, NJ, USA). The T_1/2 and AUC_last were calculated using a linear trapezoidal linear interpolation method; T_max were observed values. The brain to plasma AUC ratios of the compounds (Kp_brain) were calculated as follows:

The AUC_last-brain and AUC_last-plasma were each AUC_last of the brain and plasma, respectively.
Data acquisition and LC-ESI-TOF-MS operation were conducted using Analyst^® TF Version 1.6 (Sciex). MultiQuant^® Version 2.1.1 (Sciex) was used for the peak integration of SAS for quantification. PeakView^® Version 2.2 and MetabolitePilot^TM Version 2.0.2 were used for the structural elucidation of SAS metabolites.

Analyst^® TF Version 1.6 (Sciex, Foster City, CA, USA) operated with Windows^® (Microsoft) was used for instrument control and data acquisition. Peak integrations were operated by MultiQuant^® Version 2.1.1 (Sciex, Foster City, CA, USA). Calculations including peak area ratios, standard curve regressions, sample concentration values and descriptive statistics were calculated with MultiQuant^® Version 2.1.1. Pharmacokinetic calculations were performed using WinNonLin^® version 6.4 (Pharsight Corporation, Mountain View, CA, USA).

Data acquisition and LC-qTOF-MS operation was conducted using Analyst^® TF Version 1.6 (Sciex, Foster City, CA, USA). MultiQuant^® Version 2.1.1 (Sciex, Foster City, CA, USA) was used for the peak integration for Daporinad quantification. PeakView^® Version 2.2 (Sciex, Foster City, CA, USA) and MetabolitePilot™ Version 2.0.2 (Sciex, Foster City, CA, USA) were used for the structural elucidation of Daporinad metabolites. The descriptive statistics for the qualification studies were calculated with Excel 2015 (Microsoft). Pharmacokinetic parameters were calculated in a non-compartmental analysis using WinNonlin^® version 8.0.0 (Certara, Princeton, NJ, USA).