Quantifying Nitrosoureas: Comprehensive Insights into Analytical Techniques Transforming Cancer Research

Nitrosoureas (NUs) are a crucial class of antineoplastic agents widely used in chemotherapy to treat various malignancies, including brain tumors, lymphomas, and metastatic cancers. Over the past decade, the clinical application of NU-based chemotherapeutic drugs has expanded significantly, leading to their administration in a larger cohort of cancer patients. Despite their therapeutic efficacy, NUs exhibit high cytotoxicity, often resulting in severe adverse effects, including myelosuppression, nephrotoxicity, and pulmonary fibrosis. Given these challenges, developing reliable, sensitive, and precise analytical techniques is essential for accurately quantifying and monitoring these drugs in biological systems. This review provides a comprehensive overview of the analytical methodologies employed over the past forty years for the detection and quantification of five widely used nitrosourea-based anticancer drugs-carmustine (BCNU), lomustine (CCNU), semustine (methyl-CCNU), nimustine (NMT), and fotemustine (FM)-along with their metabolites. The discussion encompasses spectroscopic, chromatographic (liquid chromatography, gas chromatography, and high-performance liquid chromatography), and electroanalytical techniques utilized for the analysis of these compounds in various matrices, including biological fluids (plasma, urine, and tissue samples), pharmaceutical formulations, and environmental samples. Furthermore, advancements in hybrid analytical techniques and their potential in enhancing the selectivity and sensitivity of NU detection are explored. This review aims to provide insights into the evolution of analytical approaches for nitrosourea-based drugs, highlighting their applications in pharmacokinetics, therapeutic drug monitoring, and environmental surveillance.