A multi-analyte assay of opioids in API and drug products using HPLC and HRMS

Abstract

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.

Keywords: Adulteration; HPLC; High resolution mass spectrometry; Method development; Multi-analyte; Opioid; Surveillance.