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采用LC-MS/MS法测定人血浆中S-(+)-布洛芬(S-IBP)和R-(-)-布洛芬(R-IBP)的浓度,并应用于健康受试者体内药物动力学研究。以萘普生为内标,采用Daicel公司Chiralpak AD-3R(4.6 mm×150 mm,3.0μm)色谱柱,流动相为乙腈-0.01%甲酸水溶液(40∶60),流速为750μL·min~(-1),每个样品的分析时间为23.0 min,样品经电喷雾离子源负离子化后,通过三重四极杆串联质谱仪,在多反应监测模式下测定S-IBP和R-IBP(m/z205.1→161.0)和内标萘普生(m/z 229.1→185.0)的浓度。血浆样品前处理采用甲醇沉淀蛋白。S-IBP和R-IBP的血浆浓度在0.05~30.00μg·mL~(-1)内线性良好,定量下限为0.05μg·m L~(-1)。S-IBP批内、批间精密度(RSD)均在2.2%~4.2%以内,相对偏差(RE)在-12.0%~13.0%以内。R-IBP批内、批间精密度(RSD)均在2.0%~8.2%以内,相对偏差(RE)在-11.5%~10.6%以内。S-IBP和R-IBP血浆样品室温(25℃)放置6 h,反复冻融(-30℃)3次及冰冻(-30℃)保存47天的情况下均稳定。该分析方法简便、特异性高、灵敏度高,可用于受试者空腹口服布洛芬缓释胶囊300 mg后血浆样品中布洛芬对映体S-IBP和R-IBP的药动学研究。
The concentrations of S-(+) - ibuprofen (S-IBP) and R-IBP in human plasma were determined by LC-MS / MS and applied to healthy subjects In vivo pharmacokinetic studies. Using Naproxen as the internal standard, the column was separated on a Chiralpak AD-3R (4.6 mm × 150 mm, 3.0 μm) column with a mobile phase of acetonitrile-0.01% formic acid in water (40:60) at a flow rate of 750 μL · min ~ -1). The analysis time for each sample was 23.0 min. The samples were ionized by electrospray ionization and the S-IBP and R-IBP (m / z) were determined by triple quadrupole tandem mass spectrometry in a multi- z205.1 → 161.0) and the internal standard naproxen (m / z 229.1 → 185.0). Plasma samples were pre-treated with methanol to precipitate the protein. The plasma concentrations of S-IBP and R-IBP were good in the range of 0.05 ~ 30.00 μg · mL -1 with the lower limit of quantitation of 0.05 μg · mL -1. The intra-assay and intra-assay RSDs of S-IBP were within 2.2% -4.2% and the relative deviation (RE) was within -12.0% -13.0%. The intra-assay and intra-assay RSDs of R-IBP ranged from 2.0% to 8.2%, and the relative deviations (RE) ranged from -11.5% to 10.6%. Plasma samples of S-IBP and R-IBP were stable for 6 h at room temperature (25 ° C), 3 times repeated freezing and thawing (-30 ° C), and 47 days frozen (-30 ° C). The method is simple, specific and sensitive and can be used to study the pharmacokinetics of ibuprofen enantiomers S-IBP and R-IBP in plasma samples after oral administration of 300 mg ibuprofen sustained-release capsules.