Tamoxifen is the first line hormonal therapy for breast cancer patients as their adjuvant therapy. The antiestrogen effect of tamoxifen is highly determined by its active metabolite, endoxifen. A simultaneous quantification method of tamoxifen and endoxifen in dried blood spot (DBS) using LC-MS/MS had been fully validated in this study. Extraction the analyte and metabolite from DBS card were conducted using methanol-acetonitrile (50:50). The separation was performed on UPLC Class BEH C18 column using 0.2% formic acid - acetonitrile as the mobile phase in gradient elution mode at 0.2ml/min. The detection of the mass was performed on Waters Xevo TQD using positive electrospray ionization for tamoxifen, endoxifen, and clomiphene as the internal standard with m/z value: 372.22>72.22; 374.29>58.2; 406.28>100.17, respectively. This method was linear in the range concentration of 5-200 ng/ml for tamoxifen and 1-40 ng/ml for endoxifen with r value 0.99. The method was applied to 40 breast cancer patients, where the results lied between 40.28 and 194.10 ng/ml for tamoxifen, meanwhile for endoxifen was 1.25 and 18.02 ng/ml. It showed that there were 4 patients received less effective tamoxifen therapy based on the endoxifen threshold in DBS sample, which was 3.3 ng/ml. This method has prospect future to optimize tamoxifen therapy by measuring tamoxifen and endoxifen concentration. Keywords: Breast cancer; Dried blood spot; Endoxifen; Tamoxifen; Clomiphene; Analysis; LC-MS/MS; Validation.
Copyrights © 2018