•The assay determined BBR, SV and SVA simultaneously in rat plasma for the first time.•This was the first study investigating the pharmacokinetic DDI between simvastatin and BBR.•The results showed that simvastatin significantly enhanced systemic exposure of BBR, while BBR had no effect on the pharmacokinetic profile of simvastatin.A rapid and sensitive liquid chromatography–tandem mass spectrometric (LC–MS/MS) assay method was developed and validated for simultaneous quantification of simvastatin (SV), its metabolite simvastatin hydroxy acid (SVA) and berberine (BBR) in rat plasma. Separation was performed on Poroshell 120 EC-C18 column (4.6 × 50 mm, 2.7 μm) using gradient elution by mobile phase containing acetonitrile and 10 mM ammonium acetate (pH 4.5). Polarity switch (positive–negative–positive ionization mode) was performed in a total run time of 4.0 min. The lower limits of quantification (LLOQ) for SV, SVA and BBR were 0.10, 0.20 and 0.10 ng/mL, respectively. The response function was established for concentration range of 0.10–100 ng/mL for SV and BBR and 0.20–3000 ng/mL for SVA, with a coefficient of correlation of >0.99 for all the compounds. The proposed method was applied to the drug–drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats.

To investigate the impact of valproic acid (VPA) and genetic polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine (LTG) and VPA on LTG concentration in Chinese epileptic children.Three single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were analyzed by polymerase chain reaction-restriction fragment length polymorphism or direct DNA sequencing. The concentrations of LTG and VPA were measured by high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay, respectively. The adjusted concentration of LTG was defined as the concentration-to-dose-ratio (CDRLTG). Data analysis was performed using IBM SPSS Statistics 21.0.A total of 56 patients treated with LTG as monotherapy and 158 patients treated with LTG plus VPA were included in this study. In the polytherapy group, LTG concentration showed a good linear relationship with gender, age, daily LTG dose, VPA concentration, and UGT1A4*3 polymorphism, but had no relationship with the polymorphism of UGT2B7 -161C > T or UGT2B7*2. Moreover, LTG concentration and CDRLTG for the UGT1A4*3 were higher compared to UGT1A4*1 (LTG: 7.24 ± 3.51 vs 5.26 ± 3.27 μg/mL, p = 0.001; CDRLTG: 2.75 ± 1.02 vs 2.14 ± 0.96 μg/mL per mg/kg, p < 0.001, respectively). In the monotherapy group, there was no statistical difference between UGT1A4*3 and UGT1A4*1 in LTG concentration or CDRLTG. The patients in the polytherapy group were divided into two subgroups according to VPA concentration (lower/higher: 10–50/50–125 μg/mL). CDRLTG values of the patients carrying the UGT1A4*3 genotype were higher compared to UGT1A4*1*1 (2.86 ± 1.03 vs 2.22 ± 0.94 μg/mL per mg/kg, p = 0.001) only when the VPA concentration was higher.UGT1A4*3 polymorphism had an effect on LTG concentration only with VPA co-administration, and the effect was remarkable when VPA concentration was higher.