LC-MS/MS法测定人血浆中兰索拉唑及其代谢产物的浓度

LC-MS/MS determination of lansoprazole and its metabolites in human plasma

目的:建立测定人血浆中兰索拉唑及其代谢产物浓度的 LC-MS/MS 法。方法:色谱条件为 Diamonsil C_(18)(250mm×2.1mm,5μm),Octadacyl C_(18)(4.0mm×3.05mm)预柱;流动相:乙腈-2mmol·L^(-1)醋酸铵溶液(60:40,含0.1%甲酸);流速0.2mL·min^(-1);柱温40℃;进样量10μL。质谱条件为电喷雾电离源(ESI^-),选择性监测质荷比(m/z)为368.1/164.1(兰索拉唑),384.0/180.0(5-羟基兰索拉唑),384.0/115.9(兰索拉唑砜),364.1/188.8(吲达帕胺,内标)带负电荷的分子离子峰。样品用沉淀蛋白法处理。结果:兰索拉唑、5-羟基兰索拉唑、兰索拉唑砜的线性范围分别为10～5000,1.0～500,1.0～500ng·mL^(-1);定量下限分别为10,1.0,1.0ng·mL^(-1);提取回收率均在80%以上;批内、批间的 RSD 均小于15%。结论:该方法的血样处理过程简便、灵敏度高、专一,可用于兰索拉唑及其代谢产物的临床药动学研究。

Objective： To establish an LC - MS/MS method for the determination of lansoprazole and its metabolites 5 -hydroxy lansoprazole and lansoprazole sulphone in human plasma. Methods： LC： Use Diamonsil C18 column （250 mm× 2. 1 mm ,5μm） with preliminary column Octadecyl C 18 （4. 0 mm× 3.05 mm） ;the mobile phase consisting of acetonitrile - 2 mmol · L^ - 1 ammonium acetate solution including 0. 1% formic acid ; the flow rate was O. 2 mL ·min^-1; column temperature 40 ℃. MS： Use electrospray ionization（ ESI- ）, and selected ion mass monitoring （m/z） 368. 1/164. 1 （ lansoprazole）, 384. 0/180. 0 （ 5 - hydroxy lansoprazole）, 384.0/115.9 （ lansoprazole sulphone）, 364. 1/188.8 （indapamide, internal standard） to quantify. The plasma samples were treated with acetonitrile precipitation. Results：The linear range of lansoprazole,5 -hydroxy lansoprazole, lansoprazole sulphone were 10-5000,1.0- 500, 1.0- 500 ng· mL^-1 respectively,the lowest limit of test were 10,1.0, 1.0 ng· mL^-1 respectively. Extraction recoveries were more than 80%, within - batch RSD and between - batch RSD were less than 15%. Conclusion：This method is found to be easy, sensitive and specific. Therefore,it can be used for clinical pharmacokinetic studies of lansoprazole and its metabolites in human plasma.