Howell S R, Kotkoskie L A, Dills R L, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
J Pharm Sci. 1988 Apr;77(4):309-13. doi: 10.1002/jps.2600770405.
Salicylamide is an important model compound for use in investigations concerning drug disposition. In this study the metabolic fate of salicylamide at high doses was evaluated in male mice using HPLC methodology. The concentrations of salicylamide and its metabolites were determined in urine and in blood at various times after the administration of 2 or 4 mmol kg-1 salicylamide. Salicylamide, gentisamide, and their glucuronide and sulfate conjugates were detected. 2,3-Dihydroxybenzamide, the 3-hydroxy metabolite of salicylamide, as well as its glucuronide and sulfate conjugates, were identified and quantitated for the first time by HPLC. 2,3-Dihydroxybenzamide had previously been detected only as a minor metabolite of salicylamide by paper chromatography. However, in the present study, 18% of the salicylamide metabolites appearing in urine after either dosage of salicylamide were 3-hydroxylation products. When a previously published HPLC method for salicylamide analysis was used, 2,3-dihydroxybenzamide glucuronide coeluted with salicylamide glucuronide. The possible formation of 3-hydroxy metabolites must be evaluated in any study of drug metabolism using salicylamide as a model compound.
水杨酰胺是用于药物处置研究的重要模型化合物。在本研究中，使用高效液相色谱法评估了高剂量水杨酰胺在雄性小鼠体内的代谢命运。在给予2或4 mmol kg-1水杨酰胺后的不同时间，测定尿液和血液中水杨酰胺及其代谢物的浓度。检测到了水杨酰胺、龙胆酰胺及其葡萄糖醛酸和硫酸结合物。首次通过高效液相色谱法鉴定并定量了水杨酰胺的3-羟基代谢物2,3-二羟基苯甲酰胺及其葡萄糖醛酸和硫酸结合物。2,3-二羟基苯甲酰胺以前仅通过纸色谱法作为水杨酰胺的次要代谢物被检测到。然而，在本研究中，水杨酰胺任一剂量后出现在尿液中的水杨酰胺代谢物中有18%是3-羟基化产物。当使用先前发表的用于水杨酰胺分析的高效液相色谱法时，2,3-二羟基苯甲酰胺葡萄糖醛酸与水杨酰胺葡萄糖醛酸共洗脱。在任何以水杨酰胺为模型化合物的药物代谢研究中，都必须评估3-羟基代谢物的可能形成情况。
