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Clofazimine and bedaquiline are cornerstone drugs in contemporary all\u2010oral MDR\u2010TB regimens, yet their complex pharmacokinetics and substantial interindividual variability complicate regimen optimisation, particularly in vulnerable populations. Robust plasma\u2010based drug quantification is essential to characterise exposure\u2013response relationships and inform individualised therapy. We developed and validated a rapid, sensitive and specific liquid chromatography\u2013tandem mass spectrometry assay for quantifying these drugs in human plasma. The methods were successfully applied on plasma samples from study participants with MDR\u2010TB with or without HIV coinfection who received clofazimine and bedaquiline as part of MDR\u2010TB therapy assessing the Cmax, Tmax and AUC in both groups. The method addresses key analytical challenges posed by clofazimine's extreme lipophilicity and reliably quantifies concentrations across a broad, clinically relevant range, including potentially toxic exposures. Linearity was obtained between 0.0313 to 4.0\u2009mg\/L, and the method met bioanalytical method validation criteria along with interlab comparison with a reference laboratory, all within acceptable limits. We observed significantly lower Cmax concentrations of both drugs among HIV\u2010infected participants compared to HIV\u2010uninfected participants (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011 for clofazimine and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02 for bedaquiline), highlighting the need for therapeutic drug monitoring in this vulnerable group. This work provides a robust analytical foundation for pharmacokinetic, therapeutic drug monitoring and exposure\u2013response studies of key MDR\u2010TB drugs and supports efforts to optimise treatment outcomes, especially among people living with HIV.\n                  <\/jats:p>","DOI":"10.1002\/jms.70093","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:26:12Z","timestamp":1785389172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analytical Method Development and Validation for Clofazimine in Human Plasma and Application of LC\u2013MS\/MS Based Methods for Clofazimine and Bedaquiline in Indian MDR\u2010TB Patients Stratified by HIV Coinfection"],"prefix":"10.1002","volume":"61","author":[{"given":"Rohan V.","family":"Lokhande","sequence":"first","affiliation":[{"name":"Research Laboratories P.D. 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Robert","family":"Horsburgh","sequence":"additional","affiliation":[{"name":"Department of Global Health Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-0819","authenticated-orcid":false,"given":"Tester F.","family":"Ashavaid","sequence":"additional","affiliation":[{"name":"Research Laboratories P.D. 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