Meshitsuka Shunsuke, Koeda Tatsuya, Muro Hideki
Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science, Tottori 683-8503, Yonago, Japan.
Clin Chim Acta. 2003 Aug;334(1-2):145-51. doi: 10.1016/s0009-8981(03)00221-3.
It is known that valproate and its metabolites cause hepatotoxicity. The drug monitoring of valproate is important to determine an effective dose to keep an appropriate concentration in blood.
In a 2-dimensional (2D)-NMR spectrum of double quantum filtered correlation spectroscopy (DQF-COSY), clear correlation peaks were ascertained to be due to 3-keto-valproate, which was a beta-oxidation product of valproate.
A predominant metabolite of valproate was observed by proton NMR spectroscopy in the crude urine of a particular patient with metabolic disorder. The assignment of the signals was determined by synthesized 3-keto-valproic acid ethyl ester. The concentration of 3-keto-valproate in the urine was calculated to be 631 microg/mg creatinine by the integration of the peak of the isolated triplet methyl protons of C(5) at 1.016 ppm.
Although the NMR spectra of crude urine of the patients who took valproate were usually complicated with many metabolites, the signals of 3-keto-valproate in a DQF-COSY spectrum of the urine of patients were easily connected according to the present assignment. The NMR analysis of the urine of patients who are prescribed valproate is useful for therapeutic drug monitoring and for checking the compliance of the patients.
已知丙戊酸盐及其代谢产物会导致肝毒性。丙戊酸盐的药物监测对于确定有效剂量以维持血液中适当浓度很重要。
在双量子滤波相关光谱法（DQF - COSY）的二维（2D）核磁共振谱中，确定清晰的相关峰归因于3 - 酮丙戊酸盐，它是丙戊酸盐的β - 氧化产物。
通过质子核磁共振光谱法在一名患有代谢紊乱的特定患者的尿样中观察到丙戊酸盐的主要代谢产物。信号的归属通过合成的3 - 酮丙戊酸乙酯确定。通过对位于1.016 ppm处的C(5)的孤立三重峰甲基质子峰进行积分，计算出尿中3 - 酮丙戊酸盐的浓度为631微克/毫克肌酐。
尽管服用丙戊酸盐患者的尿样核磁共振谱通常因许多代谢产物而复杂，但根据当前的归属，患者尿液的DQF - COSY谱中3 - 酮丙戊酸盐的信号很容易关联起来。对服用丙戊酸盐患者的尿液进行核磁共振分析有助于治疗药物监测和检查患者的依从性。
