An Agile and Accurate Approach for N-Nitrosamines Detection and Quantification in Medicines by DART-MS.

N-nitrosamines (NAs) are prevalent mutagenic impurities in various consumer products. Their discovery in valsartan-containing medicines in 2018 prompted global regulatory agencies to set guidelines on their presence and permissible levels in pharmaceuticals. In order to determine the NAs content in medicines, efficient and sensitive analytical methods have been developed based on mass spectrometry techniques. Direct analysis in real time-mass spectrometry (DART-MS) has emerged as a prominent ambient ionization technique for pharmaceutical analysis due to its high-throughput capability, simplicity, and minimal sample preparation requirements. Thus, in this study DART-MS was evaluated for the screening and quantification of NAs in medicines. DART-MS analyses were conducted in positive ion mode, for both direct tablet analysis and solution analysis. The analytical performance was evaluated regarding linearity, precision, accuracy, limits of detection, and quantification. The DART-MS proved to be suitable for the determination of NAs in medicines, whether through direct tablet analysis or solution analysis. The analytical performance demonstrated linearity in the range from 1.00 to 200.00 ng mL-1, limits of quantification about 1.00 ng mL-1, precision and accuracy lower than 15%, and no significant matrix effect for six drug-related NAs. In conclusion, the DART-MS technique demonstrated to be an alternative method to determine NAs in medicines, aligning with the principles of green chemistry.

Development of a reliable method for determination of N-nitrosamines in medicines using disposable pipette extraction and HPLC-MS analysis.

This study outlines the development and optimization of an analytical method using Disposable Pipette Extraction (DPX) followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis to determine NAs in medicines. HPLC-MS analysis utilized a reversed-phase and positive mode electrospray ion source. DPX parameters were optimized through univariate and multivariate analyses, including extraction phase, desorption solvent, sample pH, equilibrium time, and extraction/desorption cycles. The optimized conditions included a C18 extraction phase, methanol desorption solvent, pH at 7, an equilibrium time of 30 seconds, 2 extraction cycles, and 5 desorption cycles. Considering this method, it was possible to achieve a sample preparation step for the analysis of NAs in medicines using a minimal amount of extraction phase, sample, and desorption solvent. Furthermore, the total extraction procedure enables the extraction of NAs in around 4 minutes with NA recovery up to 98%. Analytical performance demonstrated precision and accuracy below 15% and a quantification limit of 1 ng mL-1, meeting validation requirements set by regulations worldwide. Thus, the DPX/HPLC-MS technique offers a faster and cost-effective method for analyzing NAs in medicines compared to traditional approaches. Besides, this method reduces solvent consumption and residue generation, enhancing environmental sustainability according to green chemistry principles.

Desorption electrospray ionization and matrix-assisted laser desorption/ionization as imaging approaches for biological samples analysis.

The imaging of biological tissues can offer valuable information about the sample composition, which improves the understanding of analyte distribution in such complex samples. Different approaches using mass spectrometry imaging (MSI), also known as imaging mass spectrometry (IMS), enabled the visualization of the distribution of numerous metabolites, drugs, lipids, and glycans in biological samples. The high sensitivity and multiple analyte evaluation/visualization in a single sample provided by MSI methods lead to various advantages and overcome drawbacks of classical microscopy techniques. In this context, the application of MSI methods, such as desorption electrospray ionization-MSI (DESI-MSI) and matrix-assisted laser desorption/ionization-MSI (MALDI-MSI), has significantly contributed to this field. This review discusses the evaluation of exogenous and endogenous molecules in biological samples using DESI and MALDI imaging. It offers rare technical insights not commonly found in the literature (scanning speed and geometric parameters), making it a comprehensive guide for applying these techniques step-by-step. Furthermore, we provide an in-depth discussion of recent research findings on using these methods to study biological tissues.