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.

Oral Squamous Cell Carcinoma Lipid Evaluation in Gingiva Tissue Stored in TRIzol via Shotgun Lipidomics and MALDI Mass Spectrometry Imaging.

Oral squamous cell carcinoma (OSCC) is the prevalent type of oral cavity cancer, requiring precise, accurate, and affordable diagnosis to identify the disease in early stages, Comprehending the differences in lipid profiles between healthy and cancerous tissues encompasses great relevance in identifying biomarker candidates and enhancing the odds of successful cancer treatment. Therefore, the present study evaluates the analytical performance of simultaneous mRNA and lipid extraction in gingiva tissue from healthy patients and patients diagnosed with OSCC preserved in TRIzol reagent. The data was analyzed by partial least-squares discriminant analysis (PLS-DA) and confirmed via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The lipid extraction in TRIzol solution was linear in a range from 330 to 2000 ng mL-1, r2 > 0.99, intra and interday precision and accuracy <15%, and absolute recovery values ranging from 90 to 110%. The most important lipids for tumor classification were evaluated by MALDI-MSI, revealing that the lipids responsible for distinguishing the OSCC group are more prevalent in the cancerous tissue in contrast to the healthy group. The results exhibit the possibilities to do transcriptomic and lipidomic analyses in the same sample and point out important candidates related to the presence of OSCC.

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.

Bisphenol determination in UHT milk and packaging by paper spray ionization mass spectrometry.

This study evaluates the use of paper spray ionization mass spectrometry (PSI-MS) for rapid determination of bisphenol A (BPA) and bisphenol S (BPS) in UHT milk and milk packaging. The packages were analyzed by cutting the cartons into triangular shapes and submitting them to PSI-MS analysis. The milk samples were subjected to a simple liquid-liquid extraction and the supernatant was deposited onto a triangular paper that was subsequently used for PSI-MS analysis. In milk, BPS and BPA levels ranged from 60.0 to 150.8 ng mL-1. The LOD and LOQ values were 1.5 and 4.8 ng mL-1 for BPA, and 4.8 and 16.0 ng mL-1 for BPS, respectively. Linearity was R2 > 0.98 for both compounds. Precision values were below 20%, and recoveries close to 100%. The PSI-MS can be used as a simple, rapid, and accurate methodology to determine bisphenols in milk and milk packaging.

A fast and direct determination of bisphenol S in thermal paper samples using paper spray ionization mass spectrometry.

Concerns about human health regarding the large use of bisphenol A in thermal papers have led to its replacement by bisphenol S. Analyses of bisphenols require several sample pretreatment steps, which are laborious, expensive, and time-consuming. A paper spray ionization mass spectrometry (PSI-MS) was developed to detect and quantify bisphenol S in three different brands of thermal papers commercially available. Parameters such as paper size, and paper position relative to the mass spectrometer inlet were evaluated. The analyses were performed in selected ion monitoring mode on a linear ion trap mass spectrometer. The developed method presented absolute recovery values ranging from 92.2 to 109.04%, accuracy values from -1.2 to 9.0%, and inter assay precision from 1.8 to 5.6% and enabled LOD as low as 5 ng g-1. The concentration of bisphenol S in all of the three brands of BPA-free thermal papers evaluated ranged from 1.36 to 6.77 µg g-1, and the concentrarion of BPA ranged from 6.56 to 16.4 µg g-1 in all samples of thermal paper evaluated. The PSI-MS method described here was comparable to the conventional ones, such as liquid chromatography coupled with mass spectrometry and gas chromatography coupled with mass spectrometry described in the literature. The present study proved to be practical, fast, and efficient for the direct determination of bisphenol S in thermal papers. Furthermore, the methodology here described showed to be a promising alternative to replace the classical methods for determination of bisphenol S, due to its simplicity, and no needing of any sample pretreatment.

Lab-made solid phase microextraction phases for off line extraction and direct mass spectrometry analysis: Evaluating the extraction parameters.

The analyses of drugs and metabolites in complex matrices have been widely studied in recent years. However, due to high levels endogenous compounds and matrix complexity, these analyses require a sample pre-treatment step. To this aim, two lab-made extractive phases were integrated to probe electrospray ionization mass spectrometry (PESI-MS) technique for direct analysis of illicit drugs in biological fluids and phorbol esters in Jatropha curcas extract. The polypyrrole (PPy) phase was electropolymerized onto a platinum wire surface by cyclic voltammetry. The molecularly imprinted polymer (MIP) was synthesized and adhered onto a stainless-steel needle with epoxy resin. The PPy-PESI-MS method showed to be linear in a concentration range from 1 to 500 µg L-1, with accuracy values between -2.1 and 14%, and precision values between 0.8 and 10.8%. The MIP-PESI-MS method showed to be linear in a concentration range from 0.9 to 30 mg L-1, with accuracy values between -1.6 and -15.3%, and precision values between 4.1 and 13.5%.