中空纤维液相微萃取HPLC法测定清洁验证过程中的4种二氢吡啶类药物

Determination of four different dihydropyridines during cleaning validation by HPLC with hollow fiber liquid-phase microextraction

目的采用中空纤维液相微萃取（HF-LPME）-HPLC法测定清洁验证过程中4种痕量二氢吡啶类药物（尼群地平、尼莫地平、费乐地平、间尼索地平）的残留量。方法采用自制的中空纤维萃取装置对样品进行纯化富集、正辛醇为接受相、水为供给相,搅拌速度800 r·min^-1,萃取时间80 min。结果在优化的萃取条件下,尼群地平、尼莫地平、费乐地平的富集倍数达120倍,间尼索地平的富集倍数约100倍;尼群地平、尼莫地平、费乐地平和间尼索地平的线性范围为2-2.0×103ng·m L^-1,r2为0.9945-0.9990,平均回收率为93.0%-99.7%（RSD≤4.0%,n=9）。结论所用样品前处理方法简便、快速,有机溶剂用量少,富集倍数高,可用于清洁验证过程中二氢吡啶类药物的痕量检测。

OBJECTIVE To establish an HPLC method with hollow fiber liquid- phase microextraction（ HF- LPME） for the determination of four different trace dihydropyridines（ Nitrendipine,Nimodipine,Felodipine and m- Nisoldipine during cleaning validation）.METHODS With the homemade HF- LPME device,the extraction condition was optimized. Under the optimal extraction condition with 1- octanol as acceptor phase,aqueous solution as donor phase,and agitating at 800 r·min^- 1 for 80 min. The trace dihydropyridines were gathered. RESULTS The enrichment factors of Nitrendipine,Nimodipine and Felodipine were about 120 times,while m- Nisoldipine about 100. The analytes showed a good linear relationship in the range of 2- 2. 0 × 103ng·m L^- 1（ r2= 0. 9945- 0. 9990）,the average recoveries ranged from 93. 0% to 99. 7%（ RSD≤4. 0%,n = 9）. CONCLUSION The method is simple,rapid and very low organic solvent consumption and high enriching times. It has a great significane on the analysis of trace dihydropyridines on the cleaning validation.