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通过建立准确灵敏的LC-MS/MS法,测定8只SD大鼠,单剂量尾静脉注射(4 mL·kg-1)脉络宁注射液后,血浆中绿原酸、咖啡酸、3,4-二咖啡酰基奎宁酸(3,4-DCQA)、阿魏酸、肉桂酸的浓度,所测数据使用DASver 1.0软件进行处理,计算主要药动学参数。结果显示,绿原酸、咖啡酸、3,4-DCQA、阿魏酸、肉桂酸的线性范围分别为2.006~1 027μg·L-1(r=0.999 6),1.953~1 000μg·L-1(r=0.999 7),28.51~1.459×104μg·L-1(r=0.998 9),1.836~940.0μg·L-1(r=0.997 7),4.780~2 447μg·L-1(r=0.998 6)。方法学考察5种酚酸类成分血浆样品反复冻融3次、-75℃放置20 d、室温放置4 h以及血浆样品处理后的分析物放置24 h的稳定性均良好,日内、日间变异系数(RSD)小于5.0%,精密度和准确度等均符合生物样品分析的要求。大鼠体中绿原酸药代参数:t1/2为(49.78±12.81)min,AUC0-t为(123.55±14.82)mg·min·L-1,CL为(0.004 3±0.000 5)L·min-1;咖啡酸药代参数t1/2为(36.65±10.59)min,AUC0-t为(91.67±11.77)mg·min·L-1,CL为(0.005 7±0.000 7)L·min-1;3,4-DCQA药代参数:t1/2为(50.08±13.78)min,AUC0-t为(278.34±31.82)mg·min·L-1,CL为(0.001 6±0.000 2)L·min-1;阿魏酸药代参数t1/2为(51.39±15.52)min,AUC0-t为(34.72±4.67)mg·min·L-1,CL为(0.000 4±0.000 1)L·min-1;肉桂酸药代参数t1/2为(74.42±18.32)min,AUC0-t为(34.63±4.82)mg·min·L-1,CL为(0.007 7±0.001 1)L·min-1。该文所建立的LC-MS/MS适用于绿原酸等5种酚酸类成分的药代动力学研究。
Eight SD rats were established by accurate and sensitive LC-MS / MS method. After a single dose of Mailuoning injection (4 mL · kg-1) was injected into tail vein, plasma contents of chlorogenic acid, caffeic acid, - Dicaffeoylquinic acid (3,4-DCQA), ferulic acid, cinnamic acid concentration, the measured data using DASver 1.0 software processing, calculate the main pharmacokinetic parameters. The results showed that the linear ranges of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid were 2.006-1,027μg · L-1 (r = 0.999 6), 1.953-1,000μg · L-1 (r = 0.999 7), 28.51-1.459 × 104μg · L -1 (r = 0.998 9), 1.836-940.0μg · L -1 (r = 0.997 7), 4.780-2 447μg · L -1 (r = 0.998 6). Methodological study of five kinds of phenolic acids plasma samples were frozen and thawed three times repeatedly, at -75 ℃ for 20 days, at room temperature for 4 h and plasma samples after the treatment of the analyte for 24 h stability were good, intra-day and inter-day variation The coefficient (RSD) is less than 5.0%, and the precision and accuracy meet the requirements of biological sample analysis. The pharmacokinetics parameters of chlorogenic acid in rats were as follows: t1 / 2 was (49.78 ± 12.81) min, AUC0-t was (123.55 ± 14.82) mg · min · L-1 and CL was (0.0043 ± 0.0005) L · min-1. The parameters of caffeic acid substitution were t1 / 2 (36.65 ± 10.59) min, AUC0-t of (91.67 ± 11.77) mg · min · L-1 and CL of (0.005 7 ± 0.0007) 1; 3,4-DCQA drug substitution parameters: t1 / 2 was (50.08 ± 13.78) min, AUC0-t was (278.34 ± 31.82) mg · min · L-1 and CL was (0.001 6 ± 0.000 2) L · min-1. The pharmacokinetic parameters of ferulic acid were t1 / 2 (51.39 ± 15.52) min, AUC0-t (34.72 ± 4.67) mg · min · L-1 and CL (0.000 4 ± 0.0001) L · min -1; cinnamic acid pharmacokinetics parameters t1 / 2 was (74.42 ± 18.32) min, AUC0-t was (34.63 ± 4.82) mg · min · L-1 and CL was (0.007 7 ± 0.001 1) . The established LC-MS / MS is suitable for the pharmacokinetic study of five phenolic acids such as chlorogenic acid.