title: 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.
abstract: 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 = 0.991). 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 cross-reacting metabolites in urine but not in plasma. Therefore, the EIA can only be used for the determination of CGS 20,267 in plasma samples.
authors.affiliation: Ciba-Geigy Ltd., Pharma Research and Development, Basle, Switzerland.
authors.forename: C U
authors.initials: CU
authors.lastname: Pfister
authors.forename: M
authors.initials: M
authors.lastname: Duval
authors.forename: J
authors.initials: J
authors.lastname: Godbillon
authors.forename: G
authors.initials: G
authors.lastname: Gosset
authors.forename: D
authors.initials: D
authors.lastname: Gygax
authors.forename: F
authors.initials: F
authors.lastname: Marfil
authors.forename: A
authors.initials: A
authors.lastname: Sioufi
authors.forename: B
authors.initials: B
authors.lastname: Winkler
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000097:blood / Q000652:urine; D000918:Antibody Specificity; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007124:Immunoenzyme Techniques; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000032:analysis* / Q000097:blood / Q000652:urine; D014230:Triazoles / Q000032:analysis* / Q000097:blood / Q000652:urine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole