Liu Xiao-yan, Qu Ting-ting, Wang Ben-jie, Wei Chun-min, Yuan Gui-yan, Zhang Rui, Guo Rui-chen
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.
Biomed Chromatogr. 2008 Sep;22(9):1021-7. doi: 10.1002/bmc.1022.
A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of sodium cromoglycate (SCG) in human plasma after a nasal dose of 10.4 mg sodium cromoglycate nasal spray, using pravastatin sodium as the internal standard. The method was validated over a linear range of 0.300-20.0 ng/mL. SCG and I.S. were extracted from 1.0 mL of heparinized plasma by C(18) solid-phase extraction cartridges using methanol as eluting solvent. The dried residue was reconstituted with 100 microL of mobile phase, and 10 microL was injected onto the LC-MS/MS system. Chromatographic separation was achieved on a C(18) column (250 x 4.6 mm i.d., 5 microm particle size) with a mobile phase of methanol-acetonitrile-water (containing 2 mmol/L ammonium acetate; 42.5:42.5:15, v/v/v) at a flow rate of 0.4 mL/min. The analytes were detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 469.0 (precursor ion) to m/z 245.0 (product ion) for SCG and m/z 447.2 (precursor ion) to m/z327.1 (product ion) for pravastatin sodium (internal standard) The average recovery of SCG from human plasma was 94.88% and the lower limit of quantitation was 0.3 ng/mL. Results from a 3-day validation study demonstrated excellent precision and accuracy across the calibration range of 0.3-20 ng/mL. The method was successfully applied to the pharmacokinetic study of SCG in healthy Chinese volunteers.
建立了一种灵敏且选择性好的液相色谱 - 串联质谱（LC - MS/MS）方法，并进行了验证，用于测定鼻腔给予10.4 mg色甘酸钠鼻喷雾剂后人体血浆中的色甘酸钠（SCG），采用普伐他汀钠作为内标。该方法在0.300 - 20.0 ng/mL的线性范围内得到验证。SCG和内标物通过C(18) 固相萃取柱从1.0 mL肝素化血浆中萃取，使用甲醇作为洗脱溶剂。干燥后的残渣用100 μL流动相复溶，取10 μL注入LC - MS/MS系统。在C(18) 柱（内径250×4.6 mm，粒径5 μm）上进行色谱分离，流动相为甲醇 - 乙腈 - 水（含2 mmol/L醋酸铵；42.5:42.5:15，v/v/v），流速为0.4 mL/min。采用电喷雾电离正离子模式的三重四极杆LC - MS/MS检测分析物。在多反应监测模式下监测的离子，SCG为m/z 469.0（母离子）到m/z 245.0（子离子），普伐他汀钠（内标）为m/z 447.2（母离子）到m/z327.1（子离子）。SCG从人体血浆中的平均回收率为94.88%，定量下限为0.3 ng/mL。为期3天的验证研究结果表明，在0.3 - 20 ng/mL的校准范围内具有优异的精密度和准确度。该方法成功应用于健康中国志愿者中SCG的药代动力学研究。
