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Development, Application and Comparison of an Enzyme Immunoassay and a High-Performance Liquid Chromatography Method for the Determination of the Aromatase Inhibitor CGS 20 267 in Biological Fluids

1994; Elsevier BV; Volume: 83; Issue: 4 Linguagem: Inglês

10.1002/jps.2600830415

1520-6017

C. Pfister, M. Duval, J. Godbillon, G. Gosset, Daniel Gygax, F. Marfil, A. Sioufi, Bruce C. Winkler,

Asthma and respiratory diseases

CGS 20 267 is a new potent and selective, nonsteroidal, oral aromatase inhibitor. For its determination in human plasma and urine, an enzyme immunoassay (EIA) and an HPLC method were developed. The EIA showed good precision and accuracy (intra- and interassay variation between 3.0 and 17.7%, recoveries between 81 and 106%) and a quantitation limit of 0.7 nmol/L. A strong cross reactivity of the antibodies with the hydroxy metabolite of CGS 20 267 (CGP 44 645) was observed. The HPLC method showed a quantitation limit in plasma of 28 and 34 nmol/L for CGS 20 267 and CGP 44 645, respectively. For urine, concentrations down to 180 nmol/L (CGS 20 267) and 210 nmol/L (CGP 44 645) could be measured. A cross check between EIA and HPLC on plasma samples from healthy male volunteers or breast cancer patients treated orally with CGS 20 267 revealed an excellent correlation (slope = 0.934, intercept = 26,r= 0.99 1). However, the EIA measurements of urine samples yielded 3–25 times higher concentrations than those obtained by HPLC. Further, HPLC analysis revealed the presence of CGS 20 267 and crossreacting metabolites in urine but not in plasma. Therefore, the EIA can only be used for the determination of CGS 20 267 in plasma samples.