Nynke G. L. Jager

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A sensitive bioanalytical assay for the quantitative determination of tamoxifen and five of its phase I metabolites (N-desmethyltamoxifen, N-desmethyl-4-hydroxytamoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen and 4'-hydroxytamoxifen) in serum is described. The method has been fully validated at ranges covering steady-state serum concentrations(More)
A sensitive and selective HPLC–MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4′-hydroxytamoxifen, 4-hydroxytamoxifen, and 4′-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the(More)
The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported(More)
Tamoxifen has dramatically reduced the recurrence and mortality rate of estrogen receptor positive breast cancer. However, the efficacy of tamoxifen varies between individuals and 40% of patients will have a recurrence despite adjuvant tamoxifen treatment. Factors that predict tamoxifen efficacy would be helpful for optimizing treatment. Serum(More)
The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and (Z)-endoxifen to allow the(More)
Tamoxifen, an endocrine agent, is widely used in the treatment of estrogen receptor-positive breast cancer. It has greatly reduced disease recurrence and mortality rates of breast cancer patients, however, not all patients benefit from tamoxifen treatment because in approximately 25% to 30% of the patients the disease recurs. Many researchers have sought to(More)
BACKGROUND We developed an HPLC-MS/MS method to quantify tamoxifen (2.5-250 ng/ml) and its metabolite (Z)-endoxifen (0.5-50 ng/ml) in dried blood spots. RESULTS Extraction recovery of both analytes from Whatman DMPK-A cards was 100% and consistent over time, however, recovery of (Z)-endoxifen from Whatman 903 cards was incomplete and increased upon(More)
Two patients with squamous cell carcinoma, which accounts for 1.1% of all primary thyroid carcinomas, are described. Squamous metaplasia is the most likely etiology, but an occasional carcinoma may be derived from remnants of embryonic origin. Although squamous metaplasia has been documented in several conditions involving the thyroid, no evidence exists(More)
Initial adequate anti-infective therapy is associated with significantly improved clinical outcomes for patients with severe infections. However, in critically ill patients, several pathophysiological and/or iatrogenic factors may affect the pharmacokinetics of anti-infective agents leading to suboptimal drug exposure, in particular during the early phase(More)
Violent sexual assault such as rape typically results in extremely high levels of acute distress. The intensity of these acute psychological reactions may play a role in later recovery, with higher levels of immediate distress associated with poorer outcome. Unfortunately, post-rape forensic evidence collection procedures may serve to increase, rather than(More)