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Apixaban, a direct oral anticoagulant drug (DOAC), typically does not require routine therapeutic drug monitoring (TDM), yet recent guidelines propose its use in specific clinical scenarios. While various antifactor Xa (anti‐FXa) chromogenic assays serve as useful proxies for measuring plasma exposure to apixaban in emergencies, they lack specificity compared with chromatographic methods. This research project is intended to the development and validation of a standardized protocol of liquid chromatography–tandem mass spectrometry (LC–MS/MS) in conformity with the ICH guidelines M10 for the measurement of apixaban in both plasma and dried plasma spots (DPSs). Samples preparation included protein precipitation after the addition of a deuterated internal standard (IS), and the chromatographic separation was carried out on a Thermo Scientific™ Accucore™ Polar Premium column (50 mm × 2.1 mm, i.d. 2.6 m). The newly developed LC–MS/MS method for apixaban mesurement from both plasma and DPS resulted linear over a wide concentration range (31.25–500 ng/mL), accurate, and reproducible without matrix effects, allowing for specific and rapid quantification. Stability was assessed on quality controls and a real sample, allowing the setting up of a robust TDM protocol that was applied to five anonymized plasma samples obtained from adult patients undergoing apixaban treatment at steady‐state. In conclusion our novel LC–MS/MS method is adequate for accurate apixaban quantitation from both plasma and DPS matrixes, and may thus facilitate the guidelines suggested implementation of apixaban TDM, even in peripheral hospitals through shipment of DPS at reference laboratories. [ABSTRACT FROM AUTHOR]

Background: Dalbavancin, an antimicrobial lipoglycopeptide, is authorized in Europe for treating acute bacterial infections of the skin and skin structures in adults and pediatric patients aged 3 months and older. However, off-label dosing regimens have been proposed for various indications beyond acute bacterial infections of the skin and skin structures. This study presents a novel bioanalytical method using liquid chromatography-tandem mass spectrometry to quantify dalbavancin in low-volume plasma samples (50 μL)., Methods: The method underwent validation in accordance with international guidelines for bioanalytical method validation and was applied to 9 clinical samples obtained from pediatric and young adult patients undergoing dalbavancin therapy. Liquid chromatography-tandem mass spectrometry analyses were conducted at the G. Gaslini Institute in Genoa, Italy, utilizing an Ultimate 3000 ultra high performance liquid chromatography system coupled to a TSQ Quantiva Triple Quadrupole system (Thermo Fisher Scientific, Milan, Italy). The analytical procedure involved the addition of deuterated dalbavancin as internal standard and a rapid extraction from 50 µL of human plasma, followed by chromatographic separation on a Thermo Scientific Accucore Polar Premium column. Accurate quantification of the analyte was achieved through multiple reaction monitoring detection., Results: The assay exhibited linearity within the concentration range of 0.66-400 mcg/mL in plasma, demonstrating accuracy and reproducibility in the absence of matrix effects. Stability testing was conducted on both quality controls and real samples to establish a robust protocol under real-life conditions., Conclusions: This fast and reliable dalbavancin quantitation method could improve current pediatric clinical practice by enabling data collection for future dose recommendations in special patient populations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: to assess the clinical care impact resulting from the lack of a regional reference Centre for Paediatric Poisoning in Liguria Region (Northern Italy) and to describe the demographic and clinical characteristics of paediatric patients who accessed the Emergency Department of the 'Gaslini' Paediatric Hospital (Genoa, Liguria Region) for intoxication., Design: retrospective cohort study., Setting and Participants: patients' cases of both sexes, <18 years old, who accessed the Emergency Department of the 'Gaslini' Paediatric Hospital between January 2017 and December 2019 for intoxication., Main Outcome Measures: the Poisoning Severity Score (PSS), a simple and reliable scoring system to describe poisonings and define their severity, was used. The primary objective was pursued by investigating the percentage of cases of intoxication which followed, in the study period, a clinical care pathway inconsistent with the degree of severity ascertained through the retrospective application of the PSS. Clinical-demographic data, triage tag color-coding, and causes of intoxication of cases were also collected. Descriptive statistics were used to summarize results., Results: a total of 172 cases were identified over the study period; 28 did not meet the inclusion criteria. The final analysis involved 144 cases of intoxication, 70 were from females and 74 from males, with a median age of 3 years-old; 60% of study cases followed a clinical care pathway consistent with the intoxication severity ascertained trough the PSS, in 40% of study cases the clinical care pathway was inconsistent with PSS. The triage tag colour-code assigned was green in 16% of accesses, yellow in 82%, and red in only 2%. Out of the total of accesses, 40% of cases were attributed to drug intoxication in which the agents most involved were analgesics and sedative-hypnotic drugs, 30% to carbon monoxide and fumes poisoning, 23% to food/other substance intoxication, and 7% to alcohol intoxication., Conclusions: implementing a referral Centre for Paediatric Poisoning could potentially affect 40% of access to the Emergency Department. Further analysis should be carried out to clarify whether an integrated Telemedicine Service could guide the correct management of intoxicated paediatric patients by referring them, through the Poisoning Severity Score system, for home monitoring or immediate hospitalization, if necessary.