摘要
目的 建立高效液相色谱 质谱联用测定人血浆中米格列醇浓度的方法 ,并用于健康人体内米格列醇药物动力学研究。方法 采用MACHEREY NAGELCN色谱柱 (4. 6mm× 2 5 0mm ,5 μm) ,柱温 5 0℃ ,以乙腈 甲醇 0 . 0 2 %盐酸水溶液为流动相 ,流速0 . 80mL·min-1;质谱采用电喷雾电离源正源 (ESI+ ) ,定量分析采用选择离子监测 (SIR) ,质荷比为准分子离子峰 ;血浆样品用乙腈沉淀后 ,将乙腈挥干 ,残渣用氯仿 异丙醇提取杂质 ,磷酸液提取药物 ,外标法定量。结果 米格列醇浓度在 32~ 32. 0 0ng·mL-1内线性关系良好 ,相关系数为 0 . 9997,最低检测浓度 5ng·mL-1(S/N =3)。批内、批间RSD符合方法学要求 ,单次服用10 .0mg米格列醇片后药动学参数AUC0~ 12 ,AUC0~∞ ,cmax,tmax,t1/2 分别为 (75 92 . 7± 4 2 0 7 .4 )ng·h·mL-1,(795 7 .6± 4 4 2 5 . 7)ng·h·mL-1,(1883. 9± 912 .3)ng·mL-1,(2 . 4± 0 . 6 )h ,(2 . 5± 0 .9)h。结论 该方法稳定、灵敏度高、操作简单 ,适用于米格列醇血药浓度测定及药动学研究。
OBJECTIVE: To establish a high performance liquid chromatography- electrospray mass spectrometry method for the determination of miglitol in human plasma. To study the pharmacokinetics of miglitol in healthy volunteers. METHODS: The HPLC separation was performed on MACHEREY-NAGEL CN column (4.6 mm × 250 mm,5 μm), the column temperature was at 50°C. The mobile phase consisted of acetonitrile, methanol and 0.02% hydrochllric acid, with a flow-rate of 0.80 mL·min-1. The compound was ionized in the electrospray ionization(ESI+) ion source of the mass spectrometer and detected in the selected ion recording (SIR)mode. The samples were extracted by 0.02 mol·L-1 phosphoric acid after deposited by acetonitrile. RESULTS: The limit of detection was 5 ng·mL-1 for miglitol. The linear range was 0.032-3.20 μg·mL-1 with correlation coefficient of 0.999 7. The RSDs of the intra-day and inter-day validation were less than 15%. The results showed that AUC0-12, AUC 0-∞, cmax, tmax, t1/2 of miglitol were (7 592.7 ± 4 207.4)ng·h·mL-1, (7 957.6 ± 4 425.7)ng·h·mL-1, (1 883.9 ± 912.3)ng·mL-1, (2.4 ± 0.6)h and (2.5 ± 0.9)h, respectively. CONCLUSION: The method appeared to be accurate, sensitive, simple and is suitable for the determination of miglitol in human plasma and pharmacokinetic study.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2005年第1期51-53,共3页
Chinese Pharmaceutical Journal
关键词
高效液相色谱-质谱
米格列醇
药动学
Acetonitrile
Body fluids
Correlation methods
Deposition
Extraction
High performance liquid chromatography
Ionization
Mass spectrometry
Pharmacokinetics
Phosphoric acid