| Autor: |
Yasu T; Department of Medicinal Therapy Research, Pharmaceutical Education and Research Center, Meiji Pharmaceutical University, Tokyo, Japan.; Department of Pharmacy, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.; Bokutoh Hospital-Meiji Pharmaceutical University Joint Research Center, Tokyo, Japan., Nishijima R; Department of Medicinal Therapy Research, Pharmaceutical Education and Research Center, Meiji Pharmaceutical University, Tokyo, Japan., Ikuta R; Department of Clinical Laboratory, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.; Bokutoh Hospital-Meiji Pharmaceutical University Joint Research Center, Tokyo, Japan., Shirota M; Department of Pharmacy, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.; Bokutoh Hospital-Meiji Pharmaceutical University Joint Research Center, Tokyo, Japan., Iwase H; Department of Obstetrics and Gynecology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.; Bokutoh Hospital-Meiji Pharmaceutical University Joint Research Center, Tokyo, Japan. |
| Abstrakt: |
Olaparib is a small-molecule inhibitor of poly(ADP)-ribose polymerase (PARP) used as maintenance therapy for recurrent ovarian cancer and newly diagnosed advanced ovarian cancer after initial chemotherapy. An exposure-toxicity correlation has been reported between the probability of anemia, a common adverse event associated with olaparib, and the steady-state minimum plasma concentration (Cmin) as well as the predicted maximum plasma concentration (Cmax). On the other hand, olaparib exhibits high interpatient variability with regard to the area under the concentration-time curve, Cmax, and Cmin. Therefore, we developed a simple and sensitive assay based on high-performance liquid chromatography with ultraviolet light (HPLC-UV) for the therapeutic drug monitoring of olaparib. The analysis was performed on an octadecylsilyl column with a mobile phase consisting of 0.5% KH 2 PO 4 (pH 4.5) and acetonitrile (71:29, v/v), at a flow rate of 0.8 mL/min. Olaparib and an internal standard (imatinib) were well separated from the co-extracted material, with retention times of 13.6 and 11.5 min, respectively. The calibration curve for olaparib showed linearity over the concentration range of 0.10-10.0 μg/mL (r 2 = 0.9998). The intra- and inter- day validation coefficients ranged from 1.79 to 4.13% and 1.37 to 3.55%, respectively. Measurement accuracy ranged from - 6.07 to 3.26%, with a recovery rate of more than 91.06%. The developed method was then applied to evaluate the plasma olaparib concentrations in patients with ovarian cancer. Our findings demonstrate that HPLC-UV is an economical, simple, and sensitive method for clinical application and holds promise for the effective drug monitoring of olaparib during ovarian cancer treatment. |
