Cafaro Alessia, Mariani Marcello, Pigliasco Federica, Baiardi Giammarco, Barco Sebastiano, Biondi Margherita, Mesini Alessio, Russo Chiara, Saffioti Carolina, Mattioli Francesca, Castagnola Elio, Cangemi Giuliana
Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Ther Drug Monit. 2025 Jun 1;47(3):363-369. doi: 10.1097/FTD.0000000000001260. Epub 2024 Oct 10.
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).
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.
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.
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.
达巴万星是一种抗菌脂糖肽，在欧洲被批准用于治疗成人及3个月及以上儿科患者的皮肤和皮肤结构急性细菌感染。然而，对于皮肤和皮肤结构急性细菌感染以外的各种适应症，已有人提出了超说明书给药方案。本研究提出了一种使用液相色谱 - 串联质谱法来定量低体积血浆样本（50μL）中达巴万星的新型生物分析方法。
该方法按照生物分析方法验证的国际指南进行了验证，并应用于9份从接受达巴万星治疗的儿科和青年成人患者获得的临床样本。液相色谱 - 串联质谱分析在意大利热那亚的G. Gaslini研究所进行，使用的是与TSQ Quantiva三重四极杆系统（赛默飞世尔科技，意大利米兰）联用的Ultimate 3000超高效液相色谱系统。分析过程包括加入氘代达巴万星作为内标，并从50μL人血浆中快速提取，随后在赛默飞世尔科技Accucore Polar Premium柱上进行色谱分离。通过多反应监测检测实现了对分析物的准确定量。
该测定法在血浆浓度范围0.66 - 400 mcg/mL内呈线性，在不存在基质效应的情况下显示出准确性和可重复性。对质量控制品和实际样本都进行了稳定性测试，以建立在实际条件下稳健的方案。
这种快速且可靠的达巴万星定量方法可以通过为特殊患者群体未来的剂量推荐收集数据来改善当前的儿科临床实践。
