Microwave plasma torch mass spectrometry for rapid prediction of photo-thermal stability and degradation pathways of pharmaceuticals.

Photo-thermal stability is a key factor in pharmaceutical development, as light and heat can compromise drug safety and efficacy. Conventional methods such as HPLC, DSC, and GC-MS are slow, require complex pretreatment, and often treat photolysis and thermolysis separately. Here, we demonstrate microwave plasma torch mass spectrometry (MPT-MS) as a rapid, pretreatment-free approach for simultaneous analysis of photo-thermal stability and degradation pathways. Using direct desorption/ionization of intact tablets, six pharmaceuticals: chlorpheniramine, ornidazole, metronidazole, tinidazole, acetaminophen, and theophylline, were analyzed on average in 2 min with milligram-level sample consumption. Their stability order matched reported thermal decomposition data, validating the method. MPT-MS revealed unique photo-thermal fragmentation patterns, including nitroimidazole-specific [M + H-29]+ ions not accessible by electrospray ionization. The more MPT power the pharmaceutical molecules require to reach 80% abundance of the precursor ion, the more stable the pharmaceuticals are. The technique also resolved stability differences among isomers such as xylenes and nitrobenzenes. These results highlight MPT-MS as a powerful high-throughput tool for rapid screening of drug candidates, providing both stability ranking and mechanistic insight.