Advancing drug safety and mitigating health concerns: High-resolution mass spectrometry in the levothyroxine case study

• DOI: 10.1016/j.jpha.2024.100970
• Publication Date: 2024-03-28T18:08:39Z
• Authors: Hana Chmelařová; Maria Carmen Cata...; Jean-Christophe G...; František Švec; Lucie Nováková
• Keywords: Levothyroxine; Excipient; Critical quality attributes; Pharmaceutical formulation

Levothyroxine is a drug with narrow therapeutic index. Changing the formulation composition or switching between pharmaceutical brands can alter bioavailability, which result in major health problems. However, increased adverse reactions have not been fully explained scientifically yet and thorough investigation of formulations needed. In this study, we used non-targeted analytical approach to examine various levothyroxine formulas detail reveal possible chemical changes. Ultra-high-performance liquid chromatography coupled data-independent acquisition high-resolution mass spectrometry (UHPLC-DIA-HRMS) was employed. UHPLC-DIA-HRMS allowed aside detection degradation products also presence non-expected components formulations. Among these, identified compounds resulting from mannitol other excipients, such as citric acid, stearate, palmitate, an excipient active ingredient, levothyroxine-lactose adduct. addition these compounds, undeclared phospholipids were found three This common quality control analysis. Revealing unexpected proved that current mechanisms do cover full complexity necessarily.