LC-MS quantification of drugs and metabolites

LC-MS analysis: Chromatographic separation was performed on a C18 column, and the qTOF (Agilent 6550) was operated in positive scanning mode as described in the supplementary materials and methods. Compounds were identified based on the retention time of chemical standards and their accurate mass (tolerance 20 ppm).

Data analysis: The MassHunter Quantitative Analysis Software (Agilent, version 7.0) was used for peak integration. Statistical analysis and plotting were performed in Matlab 2017b (MathWorks). LOQ determination, pharmacokinetic parameter estimation, and additional methods are provided in the supplementary materials and methods.