Dried blood spots voor het bepalen van de serumconcentratie van tamoxifen en zijn actieve metaboliet endoxifen

Abstract

OBJECTIVE To establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and endoxifen in order to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. The antiestrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite endoxifen, and a minimum therapeutic threshold for endoxifen in serum has been proposed. DESIGN AND METHODS Paired DBS and serum samples were obtained from 50 patients using tamoxifen and analysed using HPLC-MS/MS. Serum concentrations were calculated from DBS concentrations using the formula: calculated serum concentration = DB S concentration/Id-haematocrit] + [blood cell/serum ratio) x haematocrit). The blood cell/serum ratio was determined ex vivo by incubating a batch of whole blood spiked with both analytes and imputed as a fixed value. The average haematocrit for female adults was imputed as a fixed value. Calculated and analysed serum concentrations were compared using weighted Deming regression. RESULTS Weighted Deming regression analysis comparing 44 matching pairs of DBS and serum samples showed a proportional bias for both analytes. Serum concentrations were calculated using [Tam]s.cals = [Tam)DBS/0.779 and [End)s.cal(; = [End]DBS/0.663. Calculated serum concentrations were within 20% of analysed serum concentrations in 84 and 100% of patient samples for tamoxifen and endoxifen, respectively. CONCLUSION DBS concentrations of tamoxifen and endoxifen were equal to serum concentrations after correction for haematocrit and blood cell/serum ratio. DBS sampling can be used in clinical practice.