帕立骨化醇残留清洁分析方法的验证及应用

Validation and Application of Residual Cleaning Analytical Method for Paricalcitol

目的确定帕立骨化醇注射液在制药设备上的最大允许残留限度,并建立检测帕立骨化醇清洁残留分析方法。方法色谱柱为Kromasil 100-C18柱(250 mm×4. 6 mm,5μm),流动相为15%乙腈-乙腈(梯度洗脱),流速为1. 0 m L/min,柱温为25℃,检测波长为252 nm。结果确定最大允许残留限度为0. 13 ng/cm2,检测限和定量限分别为0. 059 ng和0. 198 ng。帕立骨化醇质量浓度在1. 98~33. 02 ng/m L范围内与峰面积线性关系良好(r=0. 999 9,n=6),采用相同的擦拭方式擦拭不同材质(包括不锈钢、有机玻璃、钢化玻璃和聚四氟乙烯),回收率为62. 4%~98. 2%;精密度、重复性、重现性试验的RSD均小于10. 0%;对照品溶液和样品溶液在5℃下储存7 d稳定。结论该方法灵敏度高,专属性强,准确度好,可用于帕立骨化醇注射液生产后设备清洁效果的评估。

Objective To determine the maximum allowable residue limit of Paricalcitol Injection on pharmaceutical equipment and to develop a new cleaning analytical method for testing the paricalcitol residual. Methods The chromatographic column was Kromasil 100-C18 column( 250 mm × 4. 6 mm,5 μm),the mobile phase was 15% acetonitrile-acetonitrile,with a gradient elution rate of 1. 0 m L/min,the column temperature was 25 ℃,and the detection wavelength was 252 nm. Results The maximum allowable residue limit was0. 13 ng/cm2;the limits of detection and quantitation were 0. 059 ng and 0. 198 ng,respectively,the mass concentration of paricalcitol had good linear relationship with the peak area in the range of 1. 98-33. 02 ng/m L( r = 0. 999 9,n = 6). Different materials( including stainless steel,plexiglass,tempered glass,and polytetrafluoroethylene) were wiped with the same wiping method and recovered. The recovery rates were 62. 4%-98. 2%,the RSDs of the precision,repeatability,and reproducibility tests were all less than 10. 0%,the reference solution and the sample solution were stable at 5 ℃ for 7 d. Conclusion This method has high sensitivity,strong specificity and good accuracy,which can be used to evaluate the cleaning effect of equipment after the production of Paricalcitol Injection.