INTRODUCTION: Organic anion transporting polypeptide 1B1 (OATP1B1) is a transporter protein that plays an important role in the pharmacokinetics of substances (its substrates), regulating their penetration into hepatocytes. The functional activity of this protein is evaluated by the transport of marker substrates, for example, atorvastatin, on cell lines overexpressing OATP1B1, such as HepG2 (human hepatocellular carcinoma). AIM: To develop and validate the technique of the quantitative determination of atorvastatin in HepG2 cell line using high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). MATERIALS AND METHODS: The study was performed on HPLC chromatograph with an MS/MS detector. The conditions of the chromatographic analysis were as follows: pre-column Selectra C18 Guard Cartridges SLC-18GDC46-5UM, chromatographic column UCT Selectra C18 4.6 mm 100 mm 5 m, 100 А column, flow velocity of 0.3 mL/min, and column thermostatic control of 35C. The volume of introduced samples was 2 L, and the analysis time was 10 min. Gradient elution mode was used: the ratios of 0.1% formic acid solution and acetonitrile were 35% and 65% for 0 and 0.3 min, 5% and 95% for 0.6 and 5 min, and 35% and 65% for 5.05 and 8 min, respectively. The retention time of atorvastatin was 4.53 min. Atorvastatin detection conditions were as follows: positive ionization mode; spray voltage,3500 V; detection mode, multiple reaction monitoring 559.30 m/z 466.20 m/z, 559.30 m/z 440.20 m/z; collision energy, 17 V; source fragmentation, 0; and gas pressure-inducing dissociation, 2 mTorr. RESULTS: The developed bioanalytical method was validated by the following parameters: linearity, selectivity, accuracy, precision, lower limit of quantity determination, sample transfer, sample stability, and matrix effect. The confirmed range of the technique in cell lysate was 0.5200 nmol/L. CONCLUSION: The results validated the technique for the quantitative determination of atorvastatin in the lysate of HepG2 cell line by HPLC-MS/MS.

(1) Background: This study was planned to assess the concentration of antihypertensive drugs (AHD) in the blood serum in patients with controlled and uncontrolled arterial hypertension (AH). (2) Methods: We assessed 46 patients with AH. Based on the results of 24 h blood pressure monitoring (ABPM), the patients were randomized into two groups. The first group consisted of the patients with controlled AH; the second group consisted of the patients with uncontrolled AH. Venous blood was taken in both groups of patients in the morning before and 2 h after taking drugs to assess the concentration of lisinopril, amlodipine, valsartan, and indapamide. (3) Results. The first group included 27 patients, and the second group 19 patients. In patients with uncontrolled AH, the median concentrations of lisinopril, indapamide, amlodipine, and valsartan before and after taking the drugs did not differ from patients who reached the target BP values. (p > 0.05). In some patients with uncontrolled and controlled (shown for the first time) AH the concentration of AHD was below the limit of quantitative determination. (4) Conclusions. The obtained results indicate that the pharmacokinetics of AHD, apparently, does not play a significant role in the development of ineffectiveness of the ongoing therapy for AH. Therapeutic drug monitoring can be used to test adherence to the treatment.

2-Ethyl-6-methyl-3-hydroxypyridine succinate (EMHPS, Mexidol) is an original antioxidant and an anti-ischemic drug with the possibility of wide applications in the complex therapy of diseases, accompanied by the development of oxidative stress and ischemia; for example, ischemic stroke, chronic cerebral ischemia, and chronic heart failure. The use of EMHPS in the complex therapy of the above diseases may cause the development of drug–drug interactions, particularly pharmacokinetic interactions at the level of transporter proteins. In the present study, we evaluated the interaction of EMHPS with ABCB1 and SLCO1B1. In Caco-2 cells, it was shown that EMHPS is not a substrate of ABCB1 and that it does not affect its expression, but at the same time, it inhibits the activity of this transporter. Its inhibitory activity was inferior to verapamil—a classic inhibitor of ABCB1. In HEK293 and HEK293-SLCO1B1 cells, it was shown that EMHPS is not a substrate of SLCO1B1 either, but that it inhibited the activity of the transporter. However, its inhibitory activity was inferior to the classic inhibitor of SLCO1B1-rifampicin. Furthermore, it was found out that EMHPS does not affect SLCO1B1 expression in HepG2 cells. The approach proposed by the FDA (2020) and the International Transporter Consortium (2010) was used to assess the clinical significance of the study results. The effect of EMHPS on SLCO1B1 and the systemic inhibition of ABCB1 by EMPHS are not clinically significant, but ABCB1 inhibition by EMHPS in the gastrointestinal tract should be tested in vivo through clinical trials.