Norethisterone and ethinyloestradiol concentrations in sewage effluent, reservoirs, rivers and potable water have been estimated at less than 20 ng L-1, a value unlikely to present a significant risk to human health.

No abstract

In breast cancer patients discontinuing chronic tamoxifen therapy, the serum elimination of metabolites X, Y and E paralleled that of tamoxifen, whereas that of metabolite Z did not. The serum elimination of tamoxifen and metabolites X and B was increased by amino-glutethimide treatment, whereas that of metabolites Z, Y, and E was not.

Tamoxifen steady state can be reached in 1-2 days by the administration of a loading dose of 160 mg of tamoxifen for 2 days. Tamoxifen metabolite steady-state levels are reached regularly after 4 or more weeks during application of a loading dose. Very little tamoxifen or metabolites are excreted into the urine.

SummaryTo support the development programme of the anti-migraine drug, frovatriptan, an analytical method using HLPC-UV was validated in rat blood and subsequently cross-validated in dog and mouse blood to analyse samples generated from pre-chnical studies. The method was also evaluated in rabbit blood, however the method proved insufficiently selective/specific for this particular matrix. A need for a more sensitive method suitable for the analysis of a large number of samples to support clinical studies was identified. Advances in analytical technology over this period of development led to the development of LC-MS-MS analytical methods for human and rabbit whole blood that were appropriate for the changing requirements of each study. A summary of the respective validation data, togetherwith a discussion on the validation procedures employed, has been presented.