HTC-15 - Abstract

Abstract Title: An LC-MS/MS Method to Monitor Tamoxifen and its Metabolites in Rat for Pharmacokinetic Study
Abstract Type: Poster
Session Choice: (R)evolutions in Biopharmaceutical Analysis (KVCV)
Presenter Name: Dr Yung-Yi Cheng
Co-authors:Prof Tung-Hu Tsai
Company/Organisation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
Country: Taiwan, Republic of China

Abstract Information :

According to the statistical data published by the Ministry of Health and Welfare of the National Health insurance administration of Taiwan, the highest cancer incidence is breast cancer since 2011. Approximately 80% of all breast cancers are estrogen receptor α activity also called "ER-positive". In general, it has been reported that more than 67% of breast cancers are sensitive to tamoxifen therapy. Therefore, tamoxifen is the first-line cancer chemotherapy drug for ER-positive breast cancer. The present study focuses on to develop a convenient, rapid, and sensitive UHPLC-MS/MS method for pharmacokinetic studies of tamoxifen and its metabolites in rodent model. Detection was accessed by using a triple quadrupole tandem mass spectrometer in the selected reaction monitoring mode at [M+H]+ ion m/z 372.29 → 72.02 for tamoxifen, [M+H]+ ion m/z 372.29 → 72.02 for tamoxifen, [M+H]+ ion m/z 388.29 → 72.01 for 4-hydroxytamoxifen, [M+H]+ ion m/z 374.22 → 58.01 for E/Z-endoxifen, [M+H]+ ion m/z 358.29 → 58.01 for N-desmethyltamoxifen, and [M+H]+ ion m/z 253.17 → 238.02 for 5-methoxyflavone as the internal standard. All analytes were separated by a reverse-phase a C18 column (100 x 2.1 mm, 2.7 µm) with the mobile phase consisting of methanol-10 mM ammonium bicarbonate (20:80, v/v). All validation parameters, including the inter-day, intra-day, matrix effect, recovery, and stability in rat plasma, were acceptable according to the biological method validation guidelines developed by the FDA (2001). This method was successfully applied to a pharmacokinetic study in rats, and its results provided a constructive contribution to investigating the herb-drug interaction of concurrent use of tamoxifen and potential anticancer herbs.