At the conclusion of the December 2025 World Anti-Doping Agency (WADA) international meeting in Korea, contamination remained a contentious issue. Several high-profile cases have placed both the Agency and the public under scrutiny. Contamination often lies at the intersection of intentional doping and inadvertent exposure. Although contamination is well recognized in relation to dietary supplements, pharmaceuticals, or shared sporting equipment, exposure to prohibited substances through intimate contact-including kissing or sexual relations-has attracted increasing attention since 2009, particularly following the Richard Gasquet case, frequently cited as jurisprudential precedent. Given the author's involvement in multiple cases in which the "kissing" or "sexual contact" defense was raised, 2 recent cases with divergent decisions from sports authorities were reviewed to identify the evidentiary conditions under which a suspension may be avoided. To substantiate drug transfer during intimate contact, converging evidence is required. First, the urinary concentration of the prohibited substance must be compatible with incidental exposure. Second, the athlete's hair analysis should support the absence of exposure to a single pharmacologically active dose. Third, the partner must be identified, and their hair analysis must confirm use of the same substance detected in the athlete's urine. Finally, an interview with the partner must establish that the athlete was unaware of the partner's substance use. This analysis underscores the critical importance of the athlete's partner's cooperation in documenting the source of contamination and providing sincere, consistent evidence of their involvement as the origin of the antidoping rule violation. In cases invoking the "kissing" or "sexual contact" defense, the provision of robust and scientifically substantiated evidence regarding the source and mechanism of contamination is essential.

Therapeutic drug monitoring (TDM) is critical for optimizing drug efficacy and safety in precision medicine; however, conventional TDM methods rely on complex laboratory workflows. Consequently, there is an urgent need for fast, simple, and user-friendly technology to achieve point-of-care testing (POCT) for TDM. Aptamer-based sensors (aptasensors) have emerged as promising tools for point-of-care TDM because of their rapid response, high specificity, stability, and cost-effectiveness. This review summarizes the recent advances in aptasensor-based point-of-care TDM, analyzes current challenges, and explores future directions for enhancing clinical implementation. This comprehensive review examined aptasensor applications in TDM, emphasizing innovations in sensor design, detection limits, and real-world applicability across various drug types. The literature for this review was searched using PubMed, Web of Science, and Google Scholar, covering publications up to 2024. Search terms included "aptamer," "biosensor," and "drug monitoring." Relevant studies focusing on the application of aptasensors in point-of-care TDM were included and analyzed. Aptasensors have demonstrated significant potential for point-of-care TDM by offering rapid and accurate drug monitoring. However, key challenges including limitations in scalable fabrication processes, inadequate clinical validation in diverse populations, and environmental interferences affecting sensor robustness remain. Aptasensors hold a transformative potential for advancing point-of-care TDM, offering a pathway for personalized treatment optimization. Future efforts should prioritize rigorous clinical validation and improved stability in actual biological samples to fully realize their role in precision medicine.

The constant emergence of novel psychoactive substances (NPS) poses significant analytical challenges due to their structural diversity, low concentrations in complex biological matrices, and the limited availability of certified reference materials. This review summarizes current and emerging analytical strategies for detecting novel substances and evaluates the contribution of innovative technologies for toxicological surveillance. Studies addressing analytical techniques for NPS detection including chromatographic, spectrometric, ambient ionization, and artificial intelligence (AI)-assisted methods were systematically reviewed, with emphasis on applicability, sensitivity, and adaptability in clinical, forensic, and environmental contexts. Conventional techniques such as liquid chromatography coupled with tandem mass spectrometry and immunoassays provide reliable detection of known compounds but are limited by their targeted scope for detecting newly synthesized analogs. High-resolution mass spectrometry, nuclear magnetic resonance, and direct ionization approaches offer broader detection capabilities but remain resource-intensive. Recent advances in AI-including spectral prediction, structural classification, and de novo compound generation-offer promising new avenues for untargeted screening and early compound identification. In addition, emerging tools such as molecular networking, wastewater-based epidemiology, and portable mass spectrometry devices further enhance real-time monitoring and surveillance capacity. An integrated, adaptive analytical framework combining high-resolution mass spectrometry, ambient ionization, and AI-driven data analysis will help address the fast-evolving NPS landscape. Standardization of reference materials, harmonization across laboratories, and interdisciplinary collaboration between chemists, clinicians, and regulatory agencies will be key to improving the speed, sensitivity, and public health impact of NPS detection.

Background:Intentional sodium nitrite poisoning is an emerging trend worldwide, as it is promoted for its use in self-euthanasia. Nitrite dipstick urinalysis could potentially serve as a rapid-diagnostic tool. Urine dipstick analysis is a common point-of-care test (POCT) for the initial diagnosis of urinary tract infections. The aim of this study was to investigate nitrite dipstick urinalysis as a potential reliable POCT for the early detection of sodium nitrate poisoning.Methods:Postmortem urine samples, collected over 1 year, were prospectively analyzed for nitrite presence using a urine dipstick method. In addition, a retrospective search was conducted in the database to identify cases with suspected or confirmed sodium nitrite poisoning as the cause of death. Available urine samples from these cases were screened for the presence of nitrite.Results:Prospectively, 10 of the 420 urine samples tested positive for nitrite presence: 6 samples without any suspicion of sodium nitrite ingestion and 4 with confirmed sodium nitrite poisoning as the cause of death. In addition, in our retrospective study, 12 cases of suspected sodium nitrite poisoning were tested for nitrite presence in the urine using the dipstick. Of these, 8 tested positive for nitrite. Two of the 12 cases were later attributed to intoxication with other substances. As a control, urine samples spiked with sodium nitrite were tested using the dipstick; the pink color intensified with increasing sodium nitrite concentration.Conclusions:Nitrite dipstick urinalysis is a feasible approach for the early detection of nitrite poisoning in postmortem toxicological screening. In addition, this rapid POCT shows potential as a diagnostic tool for use in acute clinical settings in cases of suspected sodium nitrite poisoning or elevated methemoglobinemia with an unknown cause.

The concentration of antiseizure medications in vivo has a significant influence on therapeutic and adverse effects. To use antiseizure medications safely and rationally, it is crucial to establish a method of measuring their blood concentration, provide individualized medication guidance to patients, and avoid adverse effects through therapeutic drug monitoring. Therefore, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the rapid detection of antiseizure medication concentrations in blood and applied it to the monitoring of clinical antiseizure medication therapy. A Waters HPLC-ESI TQ-D with a Waters BEH C18 column (50 × 2.1 mm, 1.7 µm) was used; the blood samples were injected after protein precipitation in 50% methanol in water, and the analysis was conducted within 3.5 minutes. The ion source for mass spectrometry was an electrospray ionization source with the multiple ion reaction monitoring mode. An isotope standard was selected as the internal standard. The linearity of each epileptic drug was good in the studied concentration range (R2 > 0.9930), and the lower limit of quantification was 0.01-8.00 mcg/mL, with intraday and interday precision less than 15.00%. The recoveries of the method ranged from 91.86% to 113.97%, and the stability of the method was good and unaffected by matrix effects. The established LC-MS/MS method for the determination of antiseizure medication concentration was characterized by a simple operation procedure, short analysis time, high sensitivity, and good accuracy, providing a simple and reliable assay for the monitoring of antiseizure medication therapy.

Dried blood spot (DBS) sampling offers several advantages for therapeutic drug monitoring, including minimal invasiveness, low blood volume requirements, and potential for home sampling. However, obtaining spots of sufficient quality for reliable analysis remains a key challenge of DBS. This study aimed to evaluate the impact of enhanced visual and textual guidance on the quality of DBS by analyzing data from a prospective multicenter study involving children and adolescents. In total, 108 DBS cards from 56 children were assessed for spot quality. Rejection criteria included spot diameter <6 mm, smeared or irregularly shaped spots, and overlapping spots. Approval and rejection rates, overall success rates of DBS cards, and the most common rejection reasons were compared between the groups that did and did not receive the enhanced visual and textual support (intervention). Pre-intervention: 47.6% of the DBS cards contained at least 1 spot qualitatively acceptable for analysis, and 25.7% of all spots qualified for analysis. Post-intervention: the acceptance rates increased to 86.6% and 64.3%, respectively. In both the pre- and post-intervention groups, the most common reason for rejection was the presence of smeared or irregularly shaped spots. Continued improvements in DBS quality rely on effectively addressing challenges associated with home sampling challenges, which is critical for the seamless incorporation of DBS into clinical practice.

Tacrolimus-induced nephrotoxicity is a common adverse effect after liver transplantation. In this study, we aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to evaluate the relationships among tacrolimus dose, instantaneous and cumulative exposure, and kidney injury. Data from adult liver transplant recipients with a once-daily tacrolimus formulation were retrospectively analyzed. A sequential population PK/PD modeling approach using nonlinear mixed-effects modeling was applied. Exposure metrics included trough concentrations, the area under the concentration-time curve [area under the curve (AUC)] over a 24-hour (AUC0-24h) period, and cumulative AUC (cAUC) over 1-6 months. Renal function was defined as the change in estimated glomerular filtration rate (eGFR). Demographics, biochemical parameters, and concomitant medications were evaluated as covariates. Tacrolimus trough concentrations and eGFR measurements were obtained from a total of 44 patients for 3360 and 3504 measurements, respectively. Tacrolimus PK was best described by a one-compartment model with additive interindividual variability. Clearance was influenced by hematocrit (HCT) and postoperative days (PODs) within the first 14 days. Among exposure metrics, only cAUC over 3 months was significantly associated with renal function decline and provided the best model fit. The final PK/PD model was a direct linear model, with baseline eGFR identified as a covariate on the slope, reflecting individual susceptibility to tacrolimus-associated renal changes. Cumulative tacrolimus exposure over 3 months is a key determinant of nephrotoxicity and a valuable predictor for dose individualization. Our findings suggest that early PODs, HCT, and baseline renal function should be considered when optimizing tacrolimus therapy.

Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors may improve treatment outcomes and individualized therapy in patients with cancer. Compared with plasma, the standard TDM matrix, dried blood microsampling is associated with several advantages, including the collection of samples by the patients themselves in their home setting. This study aimed to compare dasatinib and imatinib concentrations in different blood-based matrices and to determine whether dried capillary blood collected via volumetric absorptive microsampling (VAMS) could be used as an alternative to perform TDM in patients with chronic myeloid leukemia. In addition to venous liquid whole blood, plasma, and VAMS samples (referred to as venous VAMS) prepared thereof, also fingerprick capillary VAMS samples were collected from patients receiving dasatinib or imatinib treatment by skilled personnel in a controlled environment. All samples were analyzed using validated liquid chromatography tandem mass spectrometry methods. Fifty-three patients were included in the study: 33 were treated with dasatinib and 20 with imatinib. Although a bias between dasatinib and imatinib venous VAMS and liquid blood concentrations was observed, 94% and 95% of the samples, respectively, fulfilled the 20% difference acceptance criterion. Capillary and venous concentrations were interchangeable and independent of the collection time. Using venous blood-to-plasma ratios from a prior proof-of-concept study, the VAMS results for imatinib, but not dasatinib, could reliably be converted into plasma concentrations. Through a clinical validation study, the authors demonstrated that VAMS is a viable alternative for imatinib monitoring in patients with chronic myeloid leukemia. For dasatinib, VAMS-based analysis may still allow for longitudinal follow-up (ie, provide insight into fluctuations in patients). As a next step, capillary microsampling can be integrated into the home sampling context.

Capillary blood microsampling enables the sampling of small blood volumes, making it suitable for vulnerable populations, remote collection, and repeated sampling. Owing to its minimal invasiveness, blood microsampling has emerged as an alternative to venipuncture in many fields. However, as capillary blood differs from venous blood in composition and analytes vary in their distribution between the blood cell and plasma fractions, plasma and capillary blood concentrations may differ. Because plasma is often the standard matrix for routine analyses, this discrepancy can compromise the clinicians' interpretation of capillary blood results. Hence, to ensure comparability with results obtained through plasma-based assays and reference ranges, accurate conversion to plasma concentrations may be required, which may improve the reliability and validity of microsampling-based outcomes. Despite its relevance, guidance on whether conversion is appropriate or desired and on how to translate and validate the translation of capillary blood microsampling results to plasma concentrations is lacking. To address this gap, members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) expert committees have prepared this guideline to discuss the "what, when, and how" of converting capillary to plasma concentrations and provide guidance on the decision of fit-for-purpose conversion. In addition, guidance to assess capillary blood results when the reference matrix is whole blood and to assess liquid capillary plasma results is provided. The included topics, as well as considerations and recommendations presented in this guideline, were based on a previously published dried blood spot-based IATDMCT guideline, literature review and expert opinions of the authors. Key points include the importance of conducting a comprehensive clinical validation study to fully understand capillary blood microsampling results. In addition, the performance of the conversion method should be evaluated case by case, as it depends on both the microsampling-based method and analyte of interest. Furthermore, an independent set of paired capillary and venous samples should be used to validate an established conversion formula. Finally, a key point for future studies is to focus on the clinical impact of (converted) capillary blood concentrations in comparison with decisions based on results in the reference matrix to guarantee any microsampling-based outcome.