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Determination of tamoxifen and five metabolites in plasma

1988; Elsevier BV; Volume: 6; Issue: 6-8 Linguagem: Inglês

10.1016/0731-7085(88)80136-5

1873-264X

D. Stevenson, Ray J. Briggs, D.J. Chapman, D. De Vos,

Hormonal and reproductive studies

Tamoxifen is an anti-estrogenic agent widely used in the treatment of breast cancer. It is usually administered at a dose of 20-40 mg daily. Methods for the determination of tamoxifen (TX) and its major metabolite N-desmethyltamoxifen (DMTX) in plasma have usually been based on the conversion of TX and DMTX to their fluorescent phenanthrene derivatives followed by HPLC [l] or TLC [2]. The reaction has been carried out both pre[l, 31 and post[4] column. Gas liquid chromatography-mass spectrometry has also been used [5]. The majority of previous work has been carried out on TX and DMTX only. Several other metabolites of TX have been identified [6] and attention has recently focused on these. Several thousand plasma samples have been assayed for TX and DMTX in the Authors’ laboratories [7, 81 using a modification of the method of Sternson. The aim of the present work was to adapt this method to allow the determination of four further metabolites of tamoxifen: 4-hydroxytamoxifen (B); N-desdimethyltamoxifen (Z); 4hydroxyethoxytriphenylethylethylene (Y); and 4-hydroxytriphenylethylethylene (E): the designations B, Z, Y and E are from the literature [6]. The structures are shown in Fig. 1. The method was used to determine plasma levels of these metabolites from patients at steady state taking 30 mg TX daily and also in a study of patients taking a loading dose (160 mg) of TX before taking 30 mg daily.