高效液相色譜串聯(lián)質(zhì)譜法測(cè)定人血漿中硫辛酸
發(fā)布時(shí)間:2018-04-04 07:27
本文選題:維生素B類藥物 切入點(diǎn):硫辛酸 出處:《藥物分析雜志》2015年01期
【摘要】:目的:建立LC-MS/MS法測(cè)定人血漿中硫辛酸濃度,并對(duì)口服0.2 g硫辛酸分散片后的藥代動(dòng)力學(xué)進(jìn)行研究。方法:血漿樣品以萘普生為內(nèi)標(biāo),經(jīng)乙腈沉淀蛋白后進(jìn)行LC-MS/MS分析。采用高效液相分離系統(tǒng),色譜柱為Venuseil XPB C18柱(150 mm×2.1 mm,5μm),流動(dòng)相為乙腈-10 mmol·L-1醋酸銨-甲酸(80∶20∶0.2);采用質(zhì)譜檢測(cè)系統(tǒng),ESI離子源,負(fù)離子模式,多反應(yīng)監(jiān)測(cè)(MRM)方式監(jiān)測(cè)m/z 205→m/z 171(硫辛酸)和m/z 229→m/z 170(萘普生,內(nèi)標(biāo))。結(jié)果:建立的LCMS/MS法在2.500~5 000 ng·m L-1質(zhì)量濃度范圍內(nèi),硫辛酸色譜響應(yīng)與質(zhì)量濃度相關(guān)性良好,定量下限為2.500 ng·m L-1;批內(nèi)及批間精密度RSD均小于7%,準(zhǔn)確度在96.5%~101.6%。12名受試者單次服用0.2 g硫辛酸分散片后AUC0-t為(1 816±885.6)ng·m L-1·h,AUC0-∞為(1 837±879.6)ng·m L-1·h,Cmax為(3 432±2 410)ng·m L-1,tmax為(0.45±0.44)h,t1/2為(0.45±0.18)h,MRT為(0.73±0.31)h,CL為(133.2±66.63)L·h-1,Vd為(85.60±50.98)L。結(jié)論:本測(cè)定方法靈敏準(zhǔn)確,適用于人血漿中硫辛酸濃度的測(cè)定及其藥代動(dòng)力學(xué)研究。
[Abstract]:Objective: to determine the concentration of lipoic acid in human plasma by LC-MS/MS and Study on 0.2 g oral lipoic acid dispersible tablets after pharmacokinetics. Methods: plasma samples with Nai Pusheng as the internal standard, with acetonitrile protein precipitation was analyzed by LC-MS/MS. The phase separation system with high performance liquid chromatography column Venuseil XPB column (C18 150 mm * 2.1 mm, 5 m), acetonitrile -10 mmol L-1 ammonium acetate - formic acid (80: 20: 0.2); the mass detection system, ESI ion source, negative ion mode and multiple reaction monitoring (MRM) mode of monitoring m/z 205 to m/z 171 (lipoic acid) and m/z 229 m/z (Nai Pusheng, 170, internal standard). Results: the established LCMS/MS method in 2.500~5 000 ng m L-1 concentration range, lipoic acid concentration and chromatographic response relationship between the lower limit of quantification was 2.500 ng - M L-1; the intra batch and inter batch precision of RSD are less than 7% accuracy in 96.5%~101.6%.12 single subjects Taking 0.2 g lipoic acid dispersible tablet in AUC0-t (1816 + 885.6) ng - M L-1 - H, AUC0- - (1837 + 879.6) for ng - M L-1 - H, Cmax (3432 + 2410) ng, m L-1, Tmax (0.45 + 0.44) h, t1/2 (0.45 + 0.18) h, MRT (0.73 + 0.31) h, CL (133.2 + 66.63) L, H-1, Vd (85.60 + 50.98) L. conclusion: this method is sensitive and accurate, and suitable for the determination of drug concentration of lipoic acid in human plasma and pharmacokinetic studies.
【作者單位】: 山東大學(xué)第二醫(yī)院臨床藥學(xué)部;濟(jì)南市疾病預(yù)防控制中心;山東大學(xué)藥學(xué)院;
【基金】:山東大學(xué)第二醫(yī)院青年基金項(xiàng)目資助(Y2013010075)
【分類號(hào)】:R96
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