氦质谱检测法考察定量压力气雾剂包装密封完整性

Investigation the container closure integrity of the pressurized metered dose inhalers by helium mass spectrometry

目的:建立和验证氦质谱检测法测试定量压力气雾剂(pressurized metered dose inhalers, pMDIs)容器密封系统(container closure system, CCS)的密封完整性。方法:确定pMDIs的CCS在全生命周期内最大可允许泄漏限度(maximum allowable leakage limit, MALL)。设计并制作专属化的测试腔体以及充氦装置,分别在充氦压力为高压状态(绝对压力672 kPa)和常压状态(绝对压力100 kPa)的条件下,对阴性及阳性对照样品进行检测。根据方法学验证的要求,完成了检测限、系统适用性、精密度、专属性和检测范围等指标的验证,并实现了稳定性考察期间加速3、6个月,长期3、12、24个月等各点的样品密封完整性检测。结果:在2种充氦压力条件下,方法学验证指标均符合可接受标准,稳定性样品检测结果均小于检测限。该方法能够100%检出pMDIs产品CCS等效孔径为0.095μm及以上的漏孔。结论:采用氦质谱检测方法能够快速定量考察pMDIs产品的泄漏率并证明CCS的密封完整性,具有较高的灵敏度,满足行业内对pMDIs产品质量控制的要求。

Objective:To establish and verify the helium mass spectrometry detection method to test the sealing in⁃tegrity of the container closure system(CCS)of pressurized metered dose aerosols(pMDIs).Methods:Deter⁃mined the maximum allowable leakage limit(MALL)of pMDIs of CCS in the whole life cycle.The special test chambers and helium filling devices were designed and manufactured,and helium filling devices to test the nega⁃tive and positive control samples under high pressure(absolute pressure 672 kPa)and normal pressure(absolute pressure 100 kPa)respectively.According to the requirements of methodology validation,the validation of detec⁃tion limit,system suitability,precision,specificity and detection range indicators were completed.The accelerated sample sealing integrity testing for 3,6 months and 3,12,24 months in the long-term stability inspection period was achieved.Results:Under both helium-filled pressure conditions,the methodological validation indicators were in line with the acceptable standards,and the results of the stability samples were less than the detection lim⁃its.This method can detect 100%that the equivalent pore diameter of pMDIs product CCS was 0.095μm and a⁃bove.Conclusion:The helium mass spectrometry detection method can quickly and quantitatively investigate the leakage rate of pMDIs products,prove the seal integrity of CCS with high sensitivity,and meet the industry’s re⁃quirements for pMDIs product quality control.