Tam Y K, Ke J, Coutts R T, Wyse D G, Gray M R
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Pharm Res. 1990 May;7(5):504-7. doi: 10.1023/a:1015868800614.
A method has been developed to quantify three lidocaine metabolites, N-ethylglycyl-2,6-xylidide (MEGX), glycyl-2,6-xylidide (GX), and 4-hydroxy-2,6-xylidine (4-OH-XY), and their conjugates in pooled human urine using enzymic hydrolysis. The commonly used enzymes, pure beta-glucuronidase, sulfatase, and a mixture of the two, were tested for their efficiencies in hydrolyzing the conjugates. Initially, it was found that 4-OH-XY was highly unstable after it was released from conjugates by beta-glucuronidase and the enzyme mixture. This problem was corrected by purging the sample with nitrogen prior to incubation. It has been determined that 4-OH-XY is present in human urine exclusively as its glucuronide. The percentage of MEGX in free and in conjugated forms (glucuronide, sulfate, and others) are 44.9 +/- 6.8, 16.6 +/- 4.5, 6.6 +/- 1.8, and 31.9 +/- 4.4, respectively. GX was present mostly in the free form (90.6 +/- 10.5%).
已开发出一种方法，用于通过酶促水解定量分析人混合尿液中的三种利多卡因代谢物，即N-乙基甘氨酰-2,6-二甲苯胺（MEGX）、甘氨酰-2,6-二甲苯胺（GX）和4-羟基-2,6-二甲苯胺（4-OH-XY）及其结合物。测试了常用的酶，即纯β-葡萄糖醛酸酶、硫酸酯酶以及二者的混合物，以评估它们水解结合物的效率。最初发现，β-葡萄糖醛酸酶和酶混合物将4-OH-XY从结合物中释放出来后，其稳定性很差。通过在孵育前用氮气吹扫样品，解决了这个问题。现已确定，人尿液中的4-OH-XY仅以其葡萄糖醛酸苷形式存在。MEGX游离形式和结合形式（葡萄糖醛酸苷、硫酸盐及其他）的百分比分别为44.9±6.8、16.6±4.5、6.6±1.8和31.9±4.4。GX大多以游离形式存在（90.6±10.5%）。
