Raman spectroscopy and mapping technique for the identification of expired drugs

As expired medical products can be repackaged and sold by unscrupulous counterfeiters, it is essential to find a rapid and convenient method for distinguishing expired and unexpired drugs. Standard detection methods such as high-performance liquid chromatography (HPLC) and thin-layer chromatography are complex, time-consuming, and require organic solvents (that are environmentally unfriendly). Additionally, the Pharmacopoeia publications do not include information about identifying expired drugs. In this study, we proposed a novel method for identifying expired medications based on Raman spectra and verified it using >20 types of expired (Old) and unexpired (New) drugs, each type from the same manufacturer. A portable Raman spectrometer was used to collect Raman spectra of all samples and the similarities between the Old and New drugs (S_N-O) were evaluated. Drugs with S_N-O values <0.9 were classified directly as expired drugs. For drugs with S_N-O values >0.9, the content of active pharmaceutical ingredient (API) might be so low (below or around 10 wt%) that its Raman signal is largely obscured by that of the excipients. In such cases, changes in the API content are undetectable using the portable instrument. Therefore, we adopted Raman mapping technology and established a virtual imaging map to locate areas of high API content. The similarities between the Old or New spectrum and that of the API (S_O-A and S_N-A, respectively) were calculated after removing the signal from the excipients. Our novel methods provide a precise, rapid, convenient, and environmentally friendly way to identify expired drugs that is more effective than the standard HPLC assay.