Simultaneous determination of deuterated vortioxetine and its major metabolite in human plasma by UPLC-MS/MS and application to a pharmacokinetic study in healthy volunteers.

JJH201501, a deuterated modification for multi-target antidepressant vortioxetine, is currently in phase I clinical trial. This study aimed to establish a sensitive and rapid UPLC-MS/MS method that was capable of simultaneously detecting JJH201501 and its major metabolite JJH201501-01 quantitatively in human plasma. The pretreatment was achieved by protein precipitation using 4-fold(v:v) acetonitrile with 5 ng/mL fluoxetine as internal standard precipitant. For method validation, the method was investigated in terms of the selectivity, inter- and intra-run precision and accuracy, carryover, matrix effect, extraction recovery and stability. The total running time was 3 min, and the retention time of JJH201501 and JJH201501-01 was 1.17 min and 1.05 min, respectively. The linear concentration range for JJH201501 and JJH201501-01 was 0.2 to 50 ng/mL and 0.4 to 100 ng/mL, respectively. The results showed that this method was in line with the guidelines for bioanalytical method proposed by FDA. In addition, the method was successfully applied to a plasma pharmacokinetic study of JJH201501 tablets in healthy volunteers which was part of the phase I trial.

Hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the determination of intact oxaliplatin in cells: validated and applied in colon cancer HCT-116 cell line.

Oxaliplatin is a platinum compound that is frequently prescribed for the chemotherapeutic treatment of colorectal cancer. In tumor cells, cellular uptake is the first step of oxaliplatin action. Cellular accumulation of oxaliplatin is considered to play an important role in anti-cancer efficacy. However, limited information about cellular accumulation of intact oxaliplatin is available. In this study, a sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach for the quantification of oxaliplatin in cells was developed and validated. The method allowed for a rapid and simple determination of intact oxaliplatin in cell lysate. The retention time of oxaliplatin was 3.04 min, which was achieved by applying a chromatographic gradient elution of 5 min. The lower limit of quantification (LLOQ) was 2 ng/mL and the analytical range of oxaliplatin was linear between 2-200 ng/mL. The intra-day precision and inter-day precision (RSD (relative standard deviation)) ranged from 0.52 to 7.89%, and the accuracy (RE (relative error)) was within ±â€¯4.5%. Matrix effects and recovery were acceptable. The method was successfully used for the determination of intact oxaliplatin uptake by HCT-116 colon cancer cells. Thus, our findings may prospectively support a celluar pharmacokinetic study and low concentration measurement of intact oxaliplatin in the clinic.