中空纤维离心超滤法测定血浆中氨茶碱浓度

李岑+王新宇+高敬林+石蕊++赵可新+张立娜+蒋晔

[摘要] 目的 以中空纤维离心超滤（HFCF-UF）技术为基础，建立一个准确、灵敏、简便的分析人血浆中氨茶碱浓度的方法，并应用于氨茶碱临床治疗药物监测。 方法 取500 μL血浆样品放入U型超滤管中，再加入200 μL甲醇，渦旋5 min，混匀，将中空纤维剪成15 cm的小段，对折插入U型超滤管中，离心力4000 r/min，离心15 min，得可用于进样分析的超滤液；以Diamonsil C18（150 mm×4.6 mm，5 μm）为色谱柱，以甲醇∶10 mmol/L乙酸铵缓冲溶液（20∶80）为流动相系统洗脱，流速1.0 mL/min，检测波长为275 nm，进样量为20 μL。 结果 血浆中氨茶碱浓度在0.528～52.8 μg/mL范围内线性关系良好（R2 = 0.9972），绝对回收率范围是98.1%～101.2%，RSD均小于1.7%。 结论 该方法操作简便，结果准确，回收率接近100%，不仅提高了药物分析人员的工作效率与结果的准确性，而且所需样品量少，能够满足生物样品采集时患者的耐受性，为氨茶碱的临床治疗药物监测提供了一个可靠的分析平台，同时，为进一步研究氨茶碱个体差异、制订最优给药方案等提供了有效的分析手段。

[关键词] 氨茶碱；血药浓度；中空纤维；前处理方法；治疗药物监测

[中图分类号] R969.1；R974.3 [文献标识码] A [文章编号] 1673-7210（2017）05（a）-0021-04

Determination of the concentration of aminophylline in human plasma by hollow fiber centrifugal ultrafiltration

LI Cen1 WANG Xinyu2 GAO Jinglin2 SHI Rui1 ZHAO Kexin1 ZHANG Li'na2 JIANG Ye2

1.Department of Pharmacy， CNPC Central Hospital， Heibei Province， Langfang 065000， China； 2.School of Pharmacy， Hebei Medical University， Hebei Province， Shijiazhuang 050017， China

[Abstract] Objective An accurate， sensitive and simple method was developed to determine the concentration of aminophylline （APY） in human plasma based on hollow fiber centrifugal ultrafiltration （HFCF-UF）， and was applied to detect APY of therapeutic drugs monitoring （TDM）. Methods Approximately 500 μL of plasma sample were placed into a U-glass tube， then， adding 200 μL of methanol， the solutions were mixed by vortex. Hollow fibre cut into 15 cm was placed in tube by folding， and ultrafiltrate was obtained for analysis by centrifugation at 4000 r/min for 15 min. The separation was performed on a Diamonsil C18 column （150 mm×4.6 mm， 5 μm） under an isolate elution with a mixture of methanol∶10 mmol ammonium acetate （20∶80， v/v）， the flow rate was 1.0 mL/min， the wavelength was 275 nm and the injection volume was 20 μL. Results APY showed a good linear range in 0.528-52.8 μg/mL （R2 = 0.9972）. The extraction recoveries ranged from 98.1% to 101.2% with RSD less than 1.7%. Conclusion The proposed method is simple， accurate and precise， which not only improves the working efficiency， but also ensures the accuracy of test results. What's more， the method requires a small amount of sample， increasing patient compliance. In general， the novel method applies a feasible way for the monitoring of APY in TDM， furthermore， provides a technique for researching the individual difference of APY， and optimizes individualized dosage regimen.

[Key words] Aminophylline； Plasma drug concentration； Hollow fiber； Preparation method； Therapeutic drugs monitoring