Therapeutic drug monitoring of tamoxifen using LC-MS/MS
Pharmaceutical Sciences and Pharmacogenomics Program, University of California San Francisco, San Francisco, CA, USA.Methods in molecular biology (Clifton, N.J.) (Impact Factor: 1.29). 07/2012; 902:211-22. DOI: 10.1007/978-1-61779-934-1_19
Tamoxifen is a selective estrogen receptor modulator (SERM) that is used widely in the treatment of estrogen receptor positive breast cancer (ER+). Therapeutic monitoring of tamoxifen, and its metabolites N-desmethyltamoxifen (NDTam) and 4-hydroxy-N-desmethyltamoxifen (endoxifen), may be clinically useful for guiding treatment decisions. Two significant barriers to tamoxifen efficacy are: (1) variability in conversion of tamoxifen into the potent antiestrogenic metabolite, endoxifen, and (2) poor compliance and adherence to tamoxifen therapy. Therapeutic monitoring can be used to address both of these issues. Low levels of endoxifen indicate either poor compliance or poor metabolism of tamoxifen. Low tamoxifen levels would suggest poor compliance while a low ratio of endoxifen to NDTam would be indicative of poor metabolism. Solid phase extraction of patient serum followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) detection enables rapid, accurate, detection of tamoxifen, N-desmethyltamoxifen, and endoxifen.
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ABSTRACT: Epidemiological and laboratory evidence suggests that quantification of serum or plasma levels of tamoxifen and its metabolites, 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), Z-4-hydroxytamoxifen (4HT), N-desmethyl-tamoxifen (ND-tam), is a clinically useful tool in the assessment and monitoring of breast cancer status in patients taking adjuvant tamoxifen. A liquid chromatographic mass spectrometric method (LC-MS/MS) was used to measure the blood levels of tamoxifen and its metabolites. This fully automated analytical method is specific, accurate and sensitive. The LC-MS/MS automated technique has now become a widely accepted reference method. This study analysed a randomly selected batch of blood samples from participants enrolled in a breast cancer study to compare results from this reference method in 40 samples with those obtained from a recently developed high-performance liquid chromatography (HPLC) method with fluorescence detection. The mean (SD) concentrations for the LC-MS/MS method (endoxifen 12.6 [7.5] ng/mL, tamoxifen 105  ng/mL, 4-HT 1.9 [1.0] ng/mL, ND-tam 181  ng/mL) and the HPLC method (endoxifen 13.1 [7.8] ng/mL, tamoxifen 108  ng/mL, 4-HT 1.8 [0.8] ng/mL, ND-tam 184  ng/mL) did not show any significant differences. The results confirm that the HPLC method offers an accurate and comparable alternative for the quantification of tamoxifen and tamoxifen metabolites.British journal of biomedical science 04/2014; 71(1):33-9. · 1.30 Impact Factor
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