Comprehensive Evaluation of Analytical Techniques for the Quantification of Etoposide in Various Matrices

Etoposide (ETO) is a semi-synthetic derivative of podophyllotoxin that is a common topoisomerase II inhibitor in the care of testicular cancer, small-cell lung cancer, leukemias, and lymphomas. Though the utility of ETO is extensive, it is constrained by variable bioavailability, a narrow therapeutic index, and potential for severe toxicities, which necessitate accurate quantification of ETO in pharmaceutical, clinical, and environmental applications. For more than four decades, measures of ETO have been described and developed. Spectrophotometric methods offer simplicity and low cost but lack specificity for complex matrices. High-performance liquid chromatography (HPLC) remains the reference standard, particularly when coupled with UV, fluorescence, or mass spectrometry (LC-MS or MS/MS), and also serves as the established method for pharmacokinetics and therapeutic drug monitoring. Other techniques, including capillary electrophoresis and emerging analytical methods, offer complementary advantages for resolution-challenged applications, thereby enhancing quality in ultra-trace and portable approaches. This review provides a narrative account of all aspects of these measures, specifically considering the basic operating principles, advantages, and disadvantages of each, the complexity of stability, matrix challenges, and ultra-trace measures. The future perspective is the need for greener, cost-effective, and clinically adapted clinical technologies, which will ultimately improve etoposide monitoring practices and patient outcomes.