288家医院质子泵抑制剂注射剂脱包调剂现状及对药品质量的影响分析

Current Status of Depackaging and Dispensing of Proton Pump Inhibitor Injections in 288 Hospitals and the Impact on Drug Quality

目的探讨质子泵抑制剂(PPIs)注射剂的医院脱包(脱去硬纸盒外包装)调剂现状及其对药品质量的影响。方法比较2010年版、2015年版、2020年版《中国药典》及国家药品监督管理局(NMPA)、美国食品和药物管理局(FDA)、欧洲药品管理局(EMA)官网药品说明书中PPIs注射剂贮藏条件的差异。通过问卷星设计并向全国30个省(96个市)的288家三级、二级、二级以下医院发放调查问卷,调查PPIs注射剂在医院的脱包贮藏现状。观察注射用奥美拉唑钠光照后的颜色变化,采用高效液相色谱-质谱法测定脱包后在光照下奥美拉唑的含量。结果《中国药典》要求PPIs应在遮光或凉暗处贮藏,国内上市的PPIs注射剂要求遮光贮藏的药品说明书占90.59%,要求避光贮藏的占9.41%,其中注射用奥美拉唑钠原研药规定脱包后在一般室内光照条件下有效期不超过24 h;FDA和EMA的奥美拉唑钠和艾司奥美拉唑钠注射剂药品说明书均要求现用现脱包。共回收问卷408份,有效问卷356份,有效回收率为87.25%。其中,三级医院最多(占68.54%),被调查人员主要为药师(占64.89%),76.69%的工作年限超过10年,仅48.03%接受过遮光药品贮藏管理培训。PPIs注射剂在药房、运输、病区环节脱包的分别占43.75%,52.78%,79.86%,脱包后未遮光贮藏的分别占35.71%,82.24%,77.83%;脱包后使用时长主要为3~5 d(占45.14%)。注射用奥美拉唑钠脱包后在一般室内光照条件下24 h内表面变黄,随光照时间的延长逐渐加深;连续光照30 d,奥美拉唑浓度的RSD为6.67%(>5%),光照16 d的含量较光照1 d减少了12.30%。结论在医院药品流通各环节中,PPIs注射剂提前脱包且脱包后未遮光贮藏的情况普遍存在,导致药品含量降低。建议相关部门应制订PPIs注射剂的脱包管理制度,要求现用现脱包,脱包后遮光贮藏。

Objective To investigate the depackaging status of Proton Pump Inhibitors(PPIs)for Injection in hospitals and the impact on drug quality.Methods The differences in the storage conditions of PPIs for Injection in the 2010,2015,and 2020 editions of the Chinese Pharmacopoeia,and those in the drug instructions of PPIs for Injection searched from the official websites of the National Medical Products Administration(NMPA),the Food and Drug Administration(FDA),and the European Medicines Agency(EMA)were compared.A questionnaire was designed by"Questionnaire Star"and distributed to 288 third-class,second-class,below second-class hospitals in 30 provinces(96 cities)in China to investigate the current depackaging and storage status of PPIs for Injection in hospitals.The color changes in Omeprazole Sodium for Injection after light exposed were observed,and the content of omeprazole under light exposed after depackaging was determined by the high-performance liquid chromatography-mass spectrometry(HPLC-MS)method.Results Chinese Pharmacopoeia requires that PPIs should be shielded from light or stored in a cool and dark place.Among the drug instructions of PPIs for Injection in the domestic market,90.59%of the instructions require shading storage,and 9.41%require avoiding light.The original-patented Omeprazole Sodium for Injection is required to be used within 24 h under general indoor light conditions after depackaging.In the FDA and EMA,Omeprazole Sodium for Injection and Esomeprazole Sodium for Injection are required to be used immediately after depackaging in the instructions for storage.A total of 408 survey questionnaires were collected,of which 356 were valid,with an effective rate of 87.25%.Among them,the proportion of third-class hospitals was the highest(68.54%),the surveyed personnel were mainly pharmacists(64.89%),76.69%of them have worked for more than 10 years,and only 48.03%of them have received training on the storage mangement of shading drugs.The depackaging rates of PPIs for Injections in pharmacy,during transportation,and in the ward were 43.75%,52.78%,and 79.86%,respectively;PPIs for Injections stored without shading after depackaging accounted for 35.71%,82.24%,and 77.83%,respectively;the duration from depackaging to use of PPIs for Injections was mainly 3-5 d(45.14%).The surface of Omeprazole Sodium for Injection turned yellow within 24 h under general indoor light conditions after depackaging,and gradually deepened with the extension of lighting time.The RSD of omeprazole concentration after 30 d of light exposed was 6.67%(>5%),and the content decreased by 12.30%after 16 d of light exposed compared to 1 d of light exposed.Conclusion Early depackaging of PPIs for Injections and unmasked storage after depackaging are common in all aspects of drug circulation in hospitals,which reduces the drug content.It is recommended that relevant departments should establish a management system for the depackaging of PPIs for Injections,which should be used immediately and stored in dark after depackaging.