{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:16:23Z","timestamp":1793837783130,"version":"4.6.1"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Health Commission Special Program for Clinical Research in the Healthcare Sector","award":["20224Y0378"],"award-info":[{"award-number":["20224Y0378"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Eravacycline exhibits potent activity against multidrug-resistant pathogens and holds promise for the management of hospital-acquired and ventilator-associated pneumonia (HAP\/VAP). However, sensitive and robust bioanalytical methods to quantify eravacycline in human pulmonary epithelial lining fluid (ELF) for pharmacokinetic (PK) and pulmonary penetration studies in these infections remain limited. Methodology: A simple, rapid, and sensitive LC-MS\/MS method was developed for the quantification of eravacycline in bronchoalveolar lavage fluid (BALF). Using urea as a volume normalizer, ELF concentrations were calculated from the eravacycline concentrations in BALF. This method was applied in a clinical study evaluating the pulmonary penetration after intravenous infusion in patients with HAP and VAP. Results: The developed LC-MS\/MS method exhibited good linearity in the range of 1\u2013200 ng\/mL for quantifying eravacycline in BALF. In BALF, intra-day precision ranged from 1.4% to 6.0%, and inter-day precision from 1.6% to 9.9%, with accuracy between 98.0% and 102.4%. Matrix effects were within 97.4% to 107.6% for BALF samples from six different individuals, with extraction recoveries ranging from 103.5% to 107.2%. Stability studies demonstrated that eravacycline remained stable under various conditions, including storage at room temperature, freeze\u2013thaw cycles, long-term (\u201370 \u00b0C) storage, and post-treatment handling. The method was successfully applied to clinical samples from four HAP or VAP patients, with measured eravacycline pulmonary penetration ratios of 4.29, 17.40, 5.22 and 4.70, indicating efficient pulmonary distribution. The measured eravacycline concentrations ranged from 0.0243 to 0.0436 \u03bcg\/mL in BALF. The corresponding urea-corrected ELF concentrations ranged from 0.570 to 1.617 \u03bcg\/mL. Conclusions: This study described a detailed and validated method for quantifying eravacycline concentrations in ELF from patients, providing a reliable analytical approach for investigating the pulmonary distribution of eravacycline.<\/jats:p>","DOI":"10.3390\/antibiotics14090957","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:08:17Z","timestamp":1758560897000},"page":"957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and Validation of a Rapid LC-MS\/MS Method for Quantifying Eravacycline in Epithelial Lining Fluid: Application to a Prospective Pulmonary Distribution Study in HAP\/VAP Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Jingjing","family":"He","sequence":"first","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanyang","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Center, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"},{"name":"Clinical Pharmacology Center, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-9149","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"},{"name":"Clinical Pharmacology Center, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-1502","authenticated-orcid":false,"given":"Xiaofen","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Institute of Antibiotics, National Health Commission, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1700582","DOI":"10.1183\/13993003.00582-2017","article-title":"International ERS\/ESICM\/ESCMID\/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)\/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociaci\u00f3n Latinoamericana del T\u00f3rax (ALAT)","volume":"50","author":"Torres","year":"2017","journal-title":"Eur. 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