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目的:建立测定人血浆中硫酸氨基葡萄糖浓度的方法,并考察其药动学特征。方法:采用高效液相色谱串联质谱电喷雾检测(LC-MS/MS)法,色谱柱为Phenomenex ODS,流动相为甲醇-0.2%醋酸铵-0.1%甲酸缓冲液(梯度洗脱),流速为1.0mL.min-1;电喷雾电离源,正离子模式下以选择反应监测(SRM)方式进行监测。以DAS2.0软件进行房室模型拟合,计算主要药动学参数。结果:在选定的色谱及质谱条件下,硫酸氨基葡萄糖与内标及血浆杂质分离良好,氨基葡萄糖增量浓度在8.27～165、165～8268ng.mL-1范围内线性关系良好。方法回收率为103.8%～113.7%,日内和日间RSD均<20%。健康受试者单剂量口服低、中、高剂量(500、1000、1500mg)复方硫酸氨基葡萄糖分散片后的药-时曲线符合非房室模型,主要药动学参数分别为:t1/2为(1.2±0.4)、(1.3±0.4)、(1.4±0.9)h,tma(x2.6±1.4)、(2.7±0.9)、(1.9±0.8)h,cma(x417±193)、(795±281)、(925±282)ng.mL-1,AUC0～1(01416±201)、(3366±1020)、(4033±1282)ng.h.mL-1,MRT0～1(03.2±0.7)、(3.6±0.2)、(3.3±0.6)h;多剂量口服低剂量(每次500mg,tid)复方硫酸氨基葡萄糖分散片达到稳态后,主要药动学参数为:cssma(x294±75.6)ng.mL-1,cssmi(n59.4±55.7)ng.mL-1,tma(x1.9±1.1)h,t1/(21.4±0.8)h,AUC0～1(01015±243)ng.h.mL-1,AUCs(s1000±244)ng.h.mL-1,cssa(v125±30.6)ng.mL-1,MRT0～1(02.7±0.3)。结论:本方法适用于复方硫酸氨基葡萄糖分散片人体内药动学研究。健康受试者单剂量口服本品后,氨基葡萄糖的吸收程度(AUC0～t和cmax)与剂量在试验设计的剂量范围内存在一定的线性关系;连续口服本品后,在体内基本无积蓄现象。
Objective: To establish a method to determine the concentration of glucosamine sulfate in human plasma and investigate its pharmacokinetic characteristics. Methods: High performance liquid chromatography-tandem mass spectrometry electrospray ionization (LC-MS / MS) was used. The chromatographic column was Phenomenex ODS. The mobile phase consisted of methanol-0.2% ammonium acetate-0.1% formic acid buffer 1.0mL.min-1; electrospray ionization source, positive ion mode selective reaction monitoring (SRM) way to monitor. DAS2.0 software for atrioventricular model fitting, calculate the main pharmacokinetic parameters. Results: Under the selected chromatographic and mass spectrometric conditions, glucosamine sulfate was well separated from the internal standard and plasma impurities. The linear increase of glucosamine concentration was observed in the range of 8.27-165 and 165-8268 ng · mL-1. The recovery rate of the method was 103.8% ~ 113.7%. The intra-day and inter-day RSD were less than 20%. The pharmacokinetic-time curves of single, low, medium and high dose (500, 1000 and 1500 mg) glucosamine sulfate dispersible tablets in healthy subjects were consistent with the non-compartmental model. The main pharmacokinetic parameters were t1 / 2 (1.2 ± 0.4), (1.3 ± 0.4), (1.4 ± 0.9) h, tma (x2.6 ± 1.4), (2.7 ± 0.9), (1.9 ± 0.8) h, cma (x417 ± 193) ± 281), (925 ± 282) ng.mL-1, AUC0 ~ 1 (01416 ± 201), (3366 ± 1020) and (4033 ± 1282) ng.h.mL- ), (3.6 ± 0.2) and (3.3 ± 0.6) h, respectively. The main pharmacokinetic parameters were cssma (x294 ± 75.6) after multiple doses of oral low dose (500mg, tid) compound glucosamine sulfate dispersible tablets ), and the AUC0 ~ 1 (01015 ± 243) ng / mL were significantly lower than those in the control group (P <0.05). mL.min-1, AUCs (s1000 ± 244) ng.h.mL-1, cssa (v125 ± 30.6) ng.mL-1, MRT0 ~ 1 (02.7 ± 0.3). Conclusion: This method is suitable for the pharmacokinetics of compound glucosamine sulfate dispersible tablets in human. Healthy subjects a single oral dose of this product, the absorption of glucosamine (AUC0 ~ t and cmax) and the dose in the experimental design of the dose range there is a certain linear relationship; continuous oral administration of this product in the body basically no savings .