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Background Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy.Methods: We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography.Results The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele *1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles.Conclusion CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy.

The validation of several micellar LC-based analytical methodologies was described. These methods were able to quantify quinolones in fish from fisheries, hydroxytyrosol in olive extracts and biogenic amines in anchovy sauce. The validation was performed following the requirements of official guides to provide more reliability. Two guides suggested by renowned institution are described: US FDA Guidance for Industry and EU Regulation 2002/657/EC Decision. The appropriate guide was used for each method, depending of the analyte, the matrix and the scope of sample. The calculated validation parameters were those proposed by the guide: selectivity, calibration range, linearity, LOD and LOQ, inter- and intra-day accuracy and precision, limit of decision, detection capability, robustness, recovery and stability. The methodologies were successfully validated by the selected guideline, indicating their suitability to be applied to analysis of real samples, proven to be useful to its intended purpose.

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