LC-MS/MS法测定人血浆中硫酸沙丁胺醇浓度及其药动学研究

目的:建立以高效液相色谱电喷雾串联质谱法测定人血浆中硫酸沙丁胺醇浓度的方法,并研究其在健康人体内的药动学。方法:血浆样品碱化后经乙酸乙酯萃取,再进样测定,以甲醇-5%甲酸(85∶15)为流动相,苯海拉明为内标,AgilenTC-C18柱进行分离。多反应方式检测,定量分析的离子反应分别为m/z240.3→m/z148.1(硫酸沙丁胺醇)和m/z256.1→m/z167.2(苯海拉明)。结果:沙丁胺醇检测浓度在0.2～20ng·mL-1范围内线性关系良好(r=0.9968),定量下限为0.2ng·mL-1;回收率为95.3%～98.2%,日内、日间RSD分别为3.75%～5.94%、3.15%～9.31%。健康受试者口服硫酸沙丁胺醇口腔崩解片后的药-时数据符合一级吸收的二室模型。结论:本方法简便、快速、灵敏,适用于硫酸沙丁胺醇的临床药动学研究。

Determination of Salbutamoi Sulfate in Human Plasma by LC - MS/MS and Its Pharmacokinetic Study

OBJECTIVE： To establish an LC/MS/MS method for the determination of salbutamol sulfate in human plasma and study its pharmacokinetics in healthy volunteers. METHODS： After being alkalized and then extracted by ethyl acetate, the plasma sample was separated on Agilent TC - C18 column with methanol - 5% formic acid（85 ： 15） as mobile phase and diphenhydramine as internal standard. The detection was carried out by multiple reaction monitoring （MRM） scan mode. In quantitative analysis, the ionic reaction of salbutamol sulfate was m/z 240.3→m/z 148.1 and that of diphenhydramine was m/z 256.1→m/z 167.2. RESULTS： The method was linear in the concentration range of 0.2-- 20.0 ng · mL ^-1（ r =： 0.996 8） for salbutamol sulfate, with lowest limit of quantification at 0.2 ng · mL ^-1. The recovery rate was 95.3% -98.2% ; the intraday RSD was 3.75%- 5.94% and the interday RSD was 3.15%-9.31%. The main pharmacokinetic parameters in 20 healthy volunteers after oral administration of 4.8 mg salbutamol sulfate orally disintegrating tablets were in line with the twocompartment mode of first order absorption. CONCLUSION ： The established method is simple, rapid and sensitive, and it is suitable for clinical pharmacokinetic study of salbutamol sulfate.