Matuszewski B K, Kanovsky S M, Constanzer M L, Yeh K C, Bayne W F
Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
J Pharm Sci. 1988 Oct;77(10):880-4. doi: 10.1002/jps.2600771014.
A sensitive (10 ng/mL) and specific high-performance liquid chromatographic (HPLC) assay, with electrochemical (EC) detection, for the geometric isomers of 3-hydroxy-N-(2-phenyl-2-(2-thienyl)ethenyl-5-(trifluoromethyl)benzo(b) thiophene-2-carboxamide in dog and human plasma has been developed. Both isomers strongly absorb light, leading to an efficient E in equilibrium Z photoisomerization. After iv administration of a single isomer (Z) to a dog, only the Zisomer was detected in plasma; no in vivo conversion to the E isomer was observed. However, when a mixture of the E and Z isomers (58.6:41.4) was administered in the same manner to the same dog, the E:Z ratio decreased significantly to 47.5:52.5 six hours after drug administration, indicating stereoselective disposition of the isomers. The elimination of the E isomer was found to be faster than that of the Z isomer.
已开发出一种灵敏（10 ng/mL）且特异的高效液相色谱（HPLC）法，并采用电化学（EC）检测，用于测定犬和人血浆中3-羟基-N-(2-苯基-2-(2-噻吩基)乙烯基-5-(三氟甲基)苯并(b)噻吩-2-甲酰胺的几何异构体。两种异构体均强烈吸收光，导致E型和Z型光异构体在平衡状态下有效互变。给犬静脉注射单一异构体（Z）后，血浆中仅检测到Z异构体；未观察到体内向E异构体的转化。然而，当以相同方式给同一只犬注射E和Z异构体的混合物（58.6:41.4）时，给药6小时后E:Z比率显著降至47.5:52.5，表明异构体存在立体选择性处置。发现E异构体的消除速度比Z异构体快。
