OBJECTIVE: To determine the concentration of glucosamine sulfate in human plasma, and to study the pharmacokinetics of glucosamine sulfate.METHODS: The plasma concentration of glucosamine sulfate was determined by LC-MS/MS.The determination was performed on Phenomenex ODS column with mobile phase consisted of methanol-0.2％ ammonium acetate-0.1％ formic acid buffer (gradient elution) at flow rate of 1.0 mL·min-1.Electrospray ionization (ESI) was applied and operated in positive ion mode by means of SRM.Its pharmacokinetic parameters were calculated by DAS 2.0 software.RESULTS: Glucosamine sulfate was well-separated from internal standard and plasma impurity.The linear ranges of glucosamine were 8.27～165 ng·mL-1 and 165～8 268 ng·mL-1 with recoveries of 103.8％～113.7％.The RSD of intra-day and inter-day were all lower than 20％.The plasma concentration-time curves of glucosamine sulfate fitted with the non-compartment model after single oral dose of Compound glucosamine sulfate dispersible tablets (500 mg, 1 000 mg, 1 500 mg).The pharmacokinetic parameters were:t1/2( 1.2 ± 0.4)、 (1.3 ±0.4) 、( 1.4 ± 0.9)h, tmax(2.6 ± 1.4) 、(2.7 ± 0.9) 、( 1.9 ± 0.8)h,cmax(417 ± 193) 、(795 ± 281 ) 、(925 ± 282)ng· mL-1 ,AUC0～10( 1 416 ± 201 )、(3 366 ± 1 020)、 (4 033 ± 1 282)ng·h·mL-1,MRT0～10(3.2 ± 0.7)、 (3.6 ± 0.2)、 (3.3 ± 0.6 )h, respectively.The main pharmacokinetic parameters of multiple oral-dose of Compound glucosamine sulfate dispersible tablets were as follows: cssmax(294 ± 75.6)ng·mL-1, cssmax (59.4 ± 55.7)ng· mL-1, tmax( 1.9 ± 1.1 )h, t1/2( 1.4 ± 0.8)h, AUC0～10( 1 015 ± 243)ng· h·mL-1 ,AUCss( 1 000 ± 244)ng·h·mL-1 ,cssav( 125 ±30.6)ng· mL-1, MRT0～10(2.7 ± 0.3)h, respectively.CONCLUSIONS: The method can be used for pharmacokinetic study of Compound glucosamine sulfate dispersible tablets.The values of AUC0～t and cmax are linear with the dose of Compound glucosamine sulfate dispersible tablets under experimental dosage scope.And no accumulation occurs during multiple doses.%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%醋酸按-0.1%甲酸缓冲液(梯度洗脱),流速为1.0 mL·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DAS 2.0软件进行房室模型拟合,计算主要药动学参数.结果:在选定的色谱及质语条件下,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8.27～165,165～8 268ng·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(500,1 000,1 500 mg)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:t,1/2为(1.2±0.4),(1.3±0.4),(1.4±0.9)h,max(2.6±1.4),(2.7±0.9)、(1.9±0.8)h,cmax(417±193),(795±281),(925±282)ng·mL-1,AUCo～10(1 416±201),(3 366±1020),(4 033±1 282) ng·h·mL-1,MRT0～10,(3.2±0.7),(3.6±0.2),(3.3±0.6)h;多剂量口服低剂量(每次500 mg,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:cmax ss(294±75.6)ng·mL-1,cmax ss (59.4±55.7)ng·mL-1,tmax(1.9±1.1)h,tl/2(1.4±0.8) h,AUC0～10(1 015±243) ng·h·mL-1,AUCss(1 000±244)ng·h·mL-1,Css av(125±30.6) ng· mL-1,MRT0～10(2.7±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(AUC0～1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.
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