交联聚维酮中2-吡咯烷酮的检测

Determination of 2-pyrrolidone in crospovidone

目的建立高效液相法对交联聚维酮中可能出现的杂质2-吡咯烷酮进行检测,并优化实验方法。方法采用C18色谱柱(250 mm×4.6 mm,5μm),流动相:水-乙腈-甲醇(90∶5∶5),流速:1.0 ml/min,柱温:30℃;检测波长205 nm。结果2-吡咯烷酮在0.0625~1.2500μg/ml范围内线性关系良好(r=0.999),2-吡咯烷酮加样回收率平均为99.6%(RSD=0.6%),重复性好,说明试验方法准确可靠。检出限为0.00034%,耐用性试验结果一致,不受仪器、色谱柱等客观条件影响。结论对10家企业的67批次样品进行测定,5家生产企业的样品均未检出,5家生产企业的样品均有检出,但均没有超出限度。说明交联聚维酮水洗工艺无法保证完全除去2-吡咯烷酮。

Objective To establish a high-performance liquid phase approach for determination of 2-pyrrolidone,a potential impurity in crospovidone,and to optimize the experimental process.Methods 2-pyrrolidone was detected by C18 column(250 mm×4.6 mm,5μm)with:mobile phase,water-acetonitrile-methanol(90∶5∶5);flow rate,1.0 ml/min;column temperature,30℃;detection wave length,205 nm.Results 2-pyrrolidone showed a good linear relationship within the range of 0.0625 to 1.2500μg/ml(r=0.999),and the mean recovery rate of 2-pyrrolidone was 99.6%(RSD=0.6%).The determination was well repeatable,indicating good accuracy and reliability.The detection limit was 0.00034%.The durability tests showed consistent results which were not interfered by objective conditions,such as instruments and chromatographic columns.Conclusion Sixty-seven sample batches from 10 manufacturers underwent determination of 2-pyrrolidone which were persistently negative in samples from five manufacturers,and positive in those from five others but the level did not exceed the allowable limit.This study suggests that water washing of crospovidone does not ensure complete removal of 2-pyrrolidone.