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目的:应用柱前衍生结合高效液相-荧光检测法对大鼠体内的肌肽手性转化和代谢动力学进行研究,进而探讨体内肌肽酶的作用特点。方法:采用邻苯二甲醛和N-乙酰-L-半胱氨酸为柱前手性衍生化试剂,检测大鼠血浆中L型肌肽(L-carnosine)和D型肌肽(D-carnosine)的浓度,应用非房室模型对所获得的血药浓度-时间数据进行拟合,计算药动学参数。结果:L-CAR和D-CAR在大鼠体内代谢具有明显的立体选择性,AUC0-∞分别为(5 641±448)ng.h.mL-1和(6 160±277)ng.h.mL-1(P<0.05),tmax分别为(0.75±0.02)h和(2.50±0.38)h(P<0.05),Cmax分别为(5 396±258)ng.mL-1和(1 958±192)ng.mL-1(P<0.05),CL/F分别为(13.36±1.02)L.h-1.kg-1和(12.19±0.56)L.h-1.kg-1(P<0.05)。并且D-CAR和L-CAR均未进行单向转化。结论:L-CAR和D-CAR在大鼠体内的药动学有明显的立体选择性(其差异主要应是肌肽酶对L-CAR作用的高度光学选择性)。肌肽对映体并未在氨基酸消旋酶作用下发生手性转化。
OBJECTIVE: To study the chiral transformation and metabolism kinetics of carnosine in rats by precolumn derivation combined with high performance liquid chromatography-fluorescence detection, and to explore the action characteristics of in vivo glycosaminoglycan. Methods: Phthalaldehyde and N-acetyl-L-cysteine were used as pre-column chiral derivatization reagents to detect the plasma L-carnosine and D-carnosine Concentration, the non-compartmental model was used to fit the obtained plasma concentration-time data, and the pharmacokinetic parameters were calculated. RESULTS: L-CAR and D-CAR had obvious stereoselective metabolism in rats with AUC0-∞ of (5 641 ± 448) ng.h.mL-1 and (6 160 ± 277) ng.h, respectively. (P <0.05), tmax was (0.75 ± 0.02) h and (2.50 ± 0.38) h respectively (P <0.05), Cmax was (5 396 ± 258) ng.mL-1 and (1 958 ± (P <0.05), CL / F was (13.36 ± 1.02) Lh-1.kg-1 and (12.19 ± 0.56) Lh-1.kg-1 respectively. And D-CAR and L-CAR were not unidirectional transformation. CONCLUSION: The pharmacokinetics of L-CAR and D-CAR in rats are significantly stereoselective (the difference should mainly be the high optical selectivity of the effect of carnosine on L-CAR). The carnosine enantiomer did not undergo chiral transformation under the action of amino acid racemase.