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Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.

Jager NG, Rosing H, Linn SC, Schellens JH, Beijnen JH - Breast Cancer Res. Treat. (2012)

Bottom Line: The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen.The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively.We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands. Nynke.Jager@slz.nl

ABSTRACT
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 mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.

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Ratio of the measured concentrations obtained with method 1, C1, and method 2, C2, in 75 patient samples for tamoxifen (a), N-desmethyltamoxifen (b), (Z)-endoxifen (c) and 4-hydroxytamoxifen (d). The solid line represents a ratio of 1.0 (i.e. equal measured concentrations) and the dotted lines represent the (bioanalytically accepted) ±15% deviation from method 2 in comparison with method 1
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Fig2: Ratio of the measured concentrations obtained with method 1, C1, and method 2, C2, in 75 patient samples for tamoxifen (a), N-desmethyltamoxifen (b), (Z)-endoxifen (c) and 4-hydroxytamoxifen (d). The solid line represents a ratio of 1.0 (i.e. equal measured concentrations) and the dotted lines represent the (bioanalytically accepted) ±15% deviation from method 2 in comparison with method 1

Mentions: The measured concentration of tamoxifen and N-desmethyltamoxifen in each serum sample was very similar for both methods (Fig. 2), resulting in comparable mean concentrations (Table 2). There are no tamoxifen metabolites described in the literature [6, 20] that have molecular masses similar to tamoxifen or N-desmethyltamoxifen, therefore co-elution of tamoxifen analogues with fragmentation patterns similar to tamoxifen or N-desmethyltamoxifen is not expected.


Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.

Jager NG, Rosing H, Linn SC, Schellens JH, Beijnen JH - Breast Cancer Res. Treat. (2012)

Ratio of the measured concentrations obtained with method 1, C1, and method 2, C2, in 75 patient samples for tamoxifen (a), N-desmethyltamoxifen (b), (Z)-endoxifen (c) and 4-hydroxytamoxifen (d). The solid line represents a ratio of 1.0 (i.e. equal measured concentrations) and the dotted lines represent the (bioanalytically accepted) ±15% deviation from method 2 in comparison with method 1
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3362711&req=5

Fig2: Ratio of the measured concentrations obtained with method 1, C1, and method 2, C2, in 75 patient samples for tamoxifen (a), N-desmethyltamoxifen (b), (Z)-endoxifen (c) and 4-hydroxytamoxifen (d). The solid line represents a ratio of 1.0 (i.e. equal measured concentrations) and the dotted lines represent the (bioanalytically accepted) ±15% deviation from method 2 in comparison with method 1
Mentions: The measured concentration of tamoxifen and N-desmethyltamoxifen in each serum sample was very similar for both methods (Fig. 2), resulting in comparable mean concentrations (Table 2). There are no tamoxifen metabolites described in the literature [6, 20] that have molecular masses similar to tamoxifen or N-desmethyltamoxifen, therefore co-elution of tamoxifen analogues with fragmentation patterns similar to tamoxifen or N-desmethyltamoxifen is not expected.

Bottom Line: The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen.The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively.We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands. Nynke.Jager@slz.nl

ABSTRACT
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 mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.

Show MeSH
Related in: MedlinePlus