Mass spectrometry (MS) is one of the most effective analytical methods that provide information about molecular weights and chemical structures of analytes with high sensitivity and specificity. The requirement for in situ MS analysis has increased over the years. The hindrance preventing MS from in situ applications can be overcome by the coupling of ambient mass spectrometry (AMS) techniques to portable mass spectrometers. Paper spray ionization (PSI) is a well-established and easy-to-use AMS technique. In PSI, triangular paper is used as a substrate to generate analyte ions by applying a high voltage and a spray solvent onto the paper. Coupling the simplicity of PSI to the portability of mass spectrometers may take MS out of the laboratory and make feasible the MS analysis in demanding environments. Therefore, in this review, we will discuss the state of the art, applications, and advances of the PSI technique as well as the development of portable mass spectrometer systems and the coupling of PSI to portable mass spectrometers to enable real-time field analysis.

With the advent of a new family of ionization techniques, ambient mass spectrometry (or ambient MS) was introduced as a simple way of generating ions in MS. Among them, the paper spray ionization (PS-MS) technique has demonstrated to be versatile to solve numerous problems in many areas of science. In this work, the PS-MS technique in the positive ionization mode (PS(+)-MS) was applied in two subareas of forensic chemistry: drugs of abuse and documentoscopy. In the first, the PS(+)MS technique was applied to obtain the chemical profiles of illicit drugs such as blotter papers containing 25I-NBOMe, extracts and leaves of natural cannabinoids (Δ⁹-tetrahydrocannabinol) and synthetic cannabinoids (naphthalen-1-yl-(1-butylindol-3-yl)methanone, (JWH-073); n-(adamantan-1-yl)-1-(4-fluorobutyl)-1H-indazole-3-carboxamide (5F-AKB48); 4-methyl-1-naphthyl-1-pentylindol-3-yl-methanone (JWH-122); 2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone (JWH-250); and 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210)) as well as to determine the authenticity in weight-loss herbal samples. Finally, an analytical method has been developed to quantify eight illicit drugs (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), meta-chlorophenylpiperazine (m-CPP), methamphetamine (MA), cocaine, lysergic acid diethylamide (LSD), and dimethoxybromoamphetamine (DOB)) where their limit-of-detection ranged from 0.17 to 1 ppb, with linearity R² > 0.99. The performance of the PS(+)-MS technique was also compared to other ionization sources: leaf spray mass spectrometry (LS-MS), and electrospray ionization mass spectrometry (ESI-MS). In the second part of this study, the PS(+)MS technique was successfully able to obtain the chemical profiles of different commercial blue pens. The relative intensity (RII₃₇₂) of the methylene blue dye was monitored to discriminate crossings of traces, and to date questioned documents. The chemical profile of the second generation of Brazilian banknotes (R$, reais) was also explored. In general, the PS(+)-MS technique was proved to be an excellent analytical tool in forensic chemistry, acting like a “Swiss army knife”.

Here, we proposed an analytical approach based on the use of a molecularly imprinted polymer-coated paper substrate (MIP-CPS) for paper spray ionization mass spectrometry (PS-MS) to improve its specificity. The new substrate developed was applied to detect and quantify dopamine, sarcosine, and butyric acid in synthetic human urine without derivatization or complex sample pre-treatments. The urinary levels of these metabolites can be correlated with several pathological conditions including heart disease, stress, neurological disorders, cancerous tumors, and AIDS. Calibration curves exhibited R² > 0.99 for dopamine, sarcosine, and butyric acid. LODs and LOQs were found at μg L⁻¹ (parts-per-billion) for dopamine and sarcosine, and pg L⁻¹ (parts-per-trillion) for butyric acid. Precision and accuracy showed coefficients of variation and relative errors less than 18% for almost all analyses. Recovery test results ranged between 95.5 and 117.7%. Finally, we compared the analytical performance of the MIP-CPS with a traditional paper substrate and ESI. The MIP-CPS showed a superior performance in detecting dopamine and avoiding the ionization suppression commonly observed during the analysis of complex biological samples such as urine.