Geerlof-Vidavsky Ilan, Balch Maurie, Stark Matthew, Ngo Diem, Gryniewicz-Ruzicka Connie
US Food and Drug Administration, Division of Pharmaceutical Analysis, 645 S. Newstead Avenue, Saint Louis, MO 63110, United States.
US Food and Drug Administration, Division of Pharmaceutical Analysis, 645 S. Newstead Avenue, Saint Louis, MO 63110, United States.
J Pharm Biomed Anal. 2024 Sep 15;248:116298. doi: 10.1016/j.jpba.2024.116298. Epub 2024 Jun 8.
Surveillance testing is an essential component to ensuring safe, effective, and high-quality drug products are available in the commercially marketed US supply chain. Surveillance allows the agency to assess product quality and monitor for potential adulteration of drug products being used by consumers. Opioid drug products can be adulterated to enhance the effect of the intended active ingredient. Numerous accounts have been reported where fentanyl has been used as an adulterant in illicit street drugs such as heroin, cocaine, or methamphetamine. To efficiently surveil the legitimate opioid supply chain, an analytical method with the ability to simultaneously detect, identify and quantify opioid molecules is desired. In this study, a multi-opioid protocol (MOP) using liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) technology was developed and validated for the detection and quantification of 27 opioid drugs. The MOP analytical procedure was applied to the analysis of drug substance and finished dosage forms. MOP was used to identify and quantify active pharmaceutical ingredients (API) listed on the label claim, and in the case of suspected economically motivated adulteration could identify and quantify undeclared opioid APIs. The analytical method analysis time was 16 minutes and the LOD and LOQ in full MS mode were (average) 0.3 and 0.8 ng/mL, respectively. The validation criteria parameters were satisfactory based on international guidelines (ICH). The MOP was successfully applied to the analysis of over 160 drug substances and finished products. For all samples tested in the study, their identities were confirmed, and assays met specifications. Overall, there was no evidence of illegal substitution or adulteration in any of the ingredients and products tested from the legitimate commercial marketed US supply chain.
监测检测是确保在美国商业销售供应链中提供安全、有效和高质量药品的重要组成部分。监测使该机构能够评估产品质量，并监测消费者使用的药品是否存在潜在掺假情况。阿片类药品可能会被掺假以增强预期活性成分的效果。已有大量报道称，芬太尼被用作海洛因、可卡因或甲基苯丙胺等非法街头毒品的掺假剂。为了有效地监测合法的阿片类供应链，需要一种能够同时检测、识别和定量阿片类分子的分析方法。在本研究中，开发了一种使用液相色谱-高分辨率质谱（HPLC-HRMS）技术的多阿片类分析方案（MOP），并对27种阿片类药物的检测和定量进行了验证。MOP分析程序应用于原料药和成品剂型的分析。MOP用于识别和定量标签声明中列出的活性药物成分（API），在怀疑存在经济动机掺假的情况下，还可以识别和定量未申报的阿片类API。该分析方法的分析时间为16分钟，全扫描模式下的检测限（LOD）和定量限（LOQ）（平均值）分别为0.3和0.8 ng/mL。根据国际指南（ICH），验证标准参数令人满意。MOP已成功应用于160多种原料药和成品的分析。对于研究中测试的所有样品，其身份得到确认，含量测定符合规格。总体而言，在美国合法商业销售供应链中测试的任何成分和产品中，均未发现非法替代或掺假的证据。
