Pfister C U, Duval M, Godbillon J, Gosset G, Gygax D, Marfil F, Sioufi A, Winkler B
Ciba-Geigy Ltd., Pharma Research and Development, Basle, Switzerland.
J Pharm Sci. 1994 Apr;83(4):520-4. doi: 10.1002/jps.2600830415.
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.
CGS 20,267是一种新型强效、选择性非甾体口服芳香酶抑制剂。为了测定其在人血浆和尿液中的含量，开发了一种酶免疫分析法（EIA）和一种高效液相色谱法（HPLC）。EIA显示出良好的精密度和准确度（批内和批间变异在3.0%至17.7%之间，回收率在81%至106%之间），定量限为0.7 nmol/L。观察到抗体与CGS 20,267的羟基代谢物（CGP 44,645）有强烈的交叉反应。HPLC法显示，血浆中CGS 20,267和CGP 44,645的定量限分别为28和34 nmol/L。对于尿液，可测量到低至180 nmol/L（CGS 20,267）和210 nmol/L（CGP 44,645）的浓度。对口服CGS 20,267的健康男性志愿者或乳腺癌患者的血浆样本进行EIA和HPLC交叉核对，结果显示两者具有极佳的相关性（斜率 = 0.934，截距 = 26，r = 0.991）。然而，尿液样本的EIA测量结果比HPLC法测得的浓度高3至25倍。此外，HPLC分析表明尿液中存在CGS 20,267和交叉反应代谢物，而血浆中不存在。因此，EIA仅可用于测定血浆样本中的CGS 20,267。
