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This study assessed the precision of matrix\u2010assisted laser desorption\u2010ionisation time\u2010of\u2010flight mass spectrometry (MALDI\u2010TOF MS) in detecting drug\u2010resistant TB. We developed a multiplex MALDI\u2010TOF MS detection assay that concurrently identifies 51 gene mutations for six commonly used medications: rifampicin (RFP), isoniazid (INH), levofloxacin (LVX), moxifloxacin (MOX), capreomycin (CPM) and amikacin (AMK). Subsequently, we evaluated the accuracy of the system by testing clinical sputum samples with known (<jats:italic>n<\/jats:italic>\u2009=\u200945) and unknown (<jats:italic>n<\/jats:italic>\u2009=\u2009254) minimum inhibitory concentrations (MICs), using Sanger\u2010sequenced genes as references. The detection system exhibited a minimum sensitivity of 88.00% and a specificity of 95.24% for the 45 known isolates. Similarly, for the 254 unknown samples, the detection system demonstrated sensitivity and specificity for mutations associated with each medication as follows: RFP\u2014sensitivity: 98.97%, specificity: 99.36%; INH\u2014sensitivity: 97.80%, specificity: 100.00%; LVX and MOX\u2014sensitivity: 97.14%, specificity: 100.00%; AMK and CPM\u2014sensitivity: 100.00%, specificity: 100.00%. The unknown samples also displayed favourable sensitivity and specificity values in the MIC validation as follows: RFP\u2014sensitivity: 92.39%, specificity: 92.59%; INH\u2014sensitivity: 75.21%, specificity: 99.27%; LVX\u2014sensitivity: 75.28%, specificity: 99.39%; MOX\u2014sensitivity: 73.24%, specificity: 91.26%; AMK\u2014sensitivity: 94.87%, specificity: 96.74%; CPM\u2014sensitivity: 89.47%, specificity: 95.83%. Meanwhile, our study allows for the identification of the <jats:styled-content style=\"fixed-case\"><jats:italic>Mycobacterium tuberculosis<\/jats:italic><\/jats:styled-content> complex (MTBC). The MALDI\u2010TOF MS exhibited remarkable accuracy in the detection of drug\u2010resistant TB, making it a potential alternative approach for clinical TB diagnosis.<\/jats:p>","DOI":"10.1111\/1440-1681.70038","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:15:20Z","timestamp":1745558120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reliability of Matrix\u2010Assisted Laser Desorption\u2010Ionisation Time\u2010of\u2010Flight Mass Spectrometry as a Method for Drug\u2010Resistant Tuberculosis Gene Identification"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5272-7603","authenticated-orcid":false,"given":"Kaishun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Lung Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Lung Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Lung Jiading District Central Hospital Affiliated Shanghai University of Medicine &amp; Health Sciences  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yameng","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Baichuangyi Biotechnology Co., Ltd.  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