Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace, and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC–MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 minutes. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision CVs% were lower than 20%, and bias was within ± 20%. Only four of the 95 analytes presented significant ionization suppression or enhancement (> 25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%), and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential to understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.

Over the last decades, new psychoactive substances (NPSs) have established a new pattern of drug synthesis and distribution. These compounds brought with them several challenges, including their analytical determination by known methodologies, the uncertainty of their toxicological effects, and the possible approaches used for control. In Brazil, the control of NPS started with a nominal list of proscribed compounds. But the variety of substances was so large that other strategies were implemented. Generic legislation was created as several groups began to emerge, such as phenethylamines, synthetic cathinones, and synthetic cannabinoids. The legislation also began to include salts and isomers of all listed substances and precursor chemical ingredients or plants that may be used to produce them. Those substances are known for the unpredictability of their effects, causing a wide range of symptoms, including seizures, aggression, and acute psychosis. Users under effect represent a high risk for themselves and others. In this study, we present an overview of the timeline in which NPSs were detected in Brazilian territory and the legislative approaches. A complete literature search was performed using PubMed, Scopus, the World Wide Web and Brazilian governmental websites employing relevant keywords such as NPS, legislation, and Brazil. Even with the high volume of legislative measures, the race against NPS intoxication cases and apprehensions continues to be fierce. There are limitations in the process of detection, identification, and prohibition of the substances in the country that demand a multifactorial approach, stronger public health measures, scientific research, as well as harm reduction strategies. Nevertheless, the Brazilian scenario on NPS arrival reflects a worldwide problem faced by many countries. In conclusion, it is stated that the use of multiple legislative strategies such as prohibition lists and generic controls can provide for better regulation of the NPS problem. However, this issue needs to be addressed by multiple organizations, including police departments and the public health system, and that effort needs to be coordinated and standardized for all Brazilian Federal states.