Indiana University-Purdue University Indianapolis (IUPUI) / Paper spray is an ambient ionization technique for mass spectrometry that is well-known for its ability to accomplish rapid and sensitive analyses without any need for sample preparation. This work further develops the technique in two major areas: negative ionization and drug screening. Negative ionization has always been an obstacle to electrospray-based ion sources because of its vulnerability to corona discharge, but methods are presented here to both quantify and suppress this electrical phenomenon, thus preventing it from interfering with qualitative/quantitative analyses. The validity of the discharge-suppressing method is demonstrated for both a simple screen of barbiturates and other acidic drugs (Chapter 2) and the detection and quantitation of chemical warfare agent hydrolysis products (Chapter 3). Additionally, a positive ion drug screen is applied to the analysis of postmortem blood samples (Chapter 4), achieving rapid and effective screening of 137 different drugs ranging from pharmaceuticals to drugs of abuse. The performance of this screen is also evaluated by comparing the results of the postmortem samples to those obtained using a more established series of assays. The research contained herein presents strides toward forensic application of paper spray mass spectrometry, especially in disciplines related to forensic toxicology.

<p> Illicit drug abuse is a widespread issue in the United States and worldwide. Many methods  seek to ease the analytical workload required to collect, analyze, and identify these drugs. Paper  spray-mass spectrometry (PS-MS) is one response to this analytical workload as it offers a rapid,  affordable, and simple means for drug identification by mass spectrometry. This work centers on  the use of pressure-sensitive adhesive (PSA) lined paper as a PS-MS substrate for drug recovery  and detection. The use of PSA paper as a sampling and analysis substrate has been previously  established but is expanded herein with new capabilities and applications. Chapter 2 introduces  the combination of color tests followed by PS-MS for presumptive and confirmatory drug  identification. Three color tests (cobalt thiocyanate, Simon, or Marquis) were performed on the  PSA paper with subsequent drug confirmation occurring by PS-MS. Chapter 3 examines the use  of PSA paper and PS-MS for the recovery and detection of fentanyl, fentanyl precursors, and  analogs from shipping-related surfaces and in the presence of high amounts of cutting agents. The  use of a cartridge that accommodates a full-sized PSA paper ticket was also explored for drug  detection. Chapter 4 assesses PS-MS with PSA paper on portable MS instrumentation. Analyte  recovery and carryover as well as instrument robustness were evaluated. The color test and PS-MS protocol examined in Chapter 2 was also successfully applied to a portable MS instrument.  Application of PS-MS to the portable system highlights the potential fieldability of the technique. </p>

Indiana University-Purdue University Indianapolis (IUPUI) / Paper spray - mass spectrometry (PS-MS) has been developed as a rapid and direct ionization method for qualitative and quantitative analysis of complex samples at trace levels. In this work, different sampling devices for PS-MS were investigated to improve the assay’s simplicity and sensitivity over traditional approaches. In particular, chapter two characterizes an alternate paper substrate to enhance drug detection on surfaces like asphalt, cloth, concrete, aluminum, and glass. Analysis occurs on a single spray ticket coated with pressure-sensitive adhesive (PSA), also known as Post-it notes to detect and quantify drug residues. A PS-MS method utilizing PSA paper was developed to detect a mixture of ten drugs off of various surfaces to evaluate the qualitative and quantitative capabilities of the aforementioned substrate. After the method development on a conventional linear ion trap mass spectrometer, the assay was translated for use on a portable mass spectrometer to evaluate the suitability of the pressure-sensitive adhesive paper substrate in the field in chapter three. Chapter four introduces a sampling device combined with a snap-in solid-phase extraction (SPE) column. The new cartridge design not only inherits the functions from the first iteration SPE cartridge, including extraction and preconcentration from complex samples, but also exhibits greater flexibility in volume control and ease of use for on-site sample collection.

This study addressed five key applications of paper spray mass spectrometry (PS-MS): (i) comparative analysis of the microporous substrate with the cellulose-based substrate in drug detection; (ii) detection of more than 190 fentanyl analogs with their fragmentation pattern can be implemented in the future reference for quicker, accurate and sensitive determination; (iii) exploring sweat in a fingerprint to be considered an alternate method to recognize non-invasive markers of metabolites, lipids, narcotics, and explosive residues that can be used in forensic testing applications; (iv) extending and improving better, cost-effective and quick real-time monitoring of the diseased stage using biofluid samples to obtain vastly different lipid information in viral infection such as COVID-19; and (v) mass spectral detection in chemical warfare agent (CWA) stimulant gas exposure with microporous structure absorbency capabilities in air quality monitoring. This novel synthetic material is known as Teslin® (PPG Industries), consisting of a microporous polyolefin single-layered silica matrix, can be used for precise, sensitive, selective, and rapid sample analysis with PS-MS. The Teslin® substrate provided longer activation time for samples and an active signal with a higher concentration of ion formation and mobility compared to cellulose-based papers. Direct analysis of multiple samples showed that, besides being more sensitive to the study and highly efficient with less sample size and spray solvent needed, Teslin® had less interaction with paper source molecules. For less than 60 seconds of processing time, PS-MS can be used as a rapid detection tool, with limited sample preparation requiring less than one microgram of the sample. Overall, the data in this analysis indicate the capacity of the PS-MS as an alternative approach for direct chemical analysis in many applications. Specifically, the waterproof and microporosity characteristics of Teslin® have proven its usefulness in detecting a variety of chemical components in liquid, solid, and gaseous phases without requiring any chemical treatment or substrate alteration.

Different sampling devices for paper spray - mass spectrometry (PS - MS) were investigated to improve the assay’s simplicity and sensitivity over traditional approaches. In the first one, pressure-sensitive adhesive paper was used as both sampling tool to collect drug residues on surfaces and paper substrate in PS - MS analysis. This method showed a significant improvement in drug collection on surfaces leading to low nano-gram level detection limits. Other sampling device being investigated was snap-in solid-phase extraction column, which demonstrated the ability to detect trace amounts of drugs in plasma while allowed easy transportation and the use of PS - MS automated system.