Development and validation of an LC-MS/MS method for the simultaneous determination of bedaquiline and rifabutin in human plasma

Wesley A Gray; Byron Waldorf; Manasa Geeta Rao; Brenda L Stiles; J McLeod Griffiss; Robert A Salata; Jeffrey L Blumer

doi:10.1016/j.jpba.2019.07.023

Development and validation of an LC-MS/MS method for the simultaneous determination of bedaquiline and rifabutin in human plasma

J Pharm Biomed Anal. 2019 Nov 30:176:112775. doi: 10.1016/j.jpba.2019.07.023. Epub 2019 Aug 16.

Authors

Wesley A Gray¹, Byron Waldorf¹, Manasa Geeta Rao¹, Brenda L Stiles², J McLeod Griffiss³, Robert A Salata⁴, Jeffrey L Blumer⁵

Affiliations

¹ The University of Toledo, Department of Pediatrics, 3000 Arlington Ave., Toledo, OH 43614, USA.
² Clinical Research Management, now ICON Government and Public Health Solutions, 1265 Ridge Road, Hinckley, OH 44233, USA.
³ Clinical Research Management, now ICON Government and Public Health Solutions, 1265 Ridge Road, Hinckley, OH 44233, USA. Electronic address: crapaud@loursage.org.
⁴ Case Western Reserve University Department of Medicine, 10900 Euclid Ave Cleveland, OH 44106, USA; Professor and Chair, Case Western Reserve University, Department of Medicine, USA.
⁵ The University of Toledo, Department of Pediatrics, 3000 Arlington Ave., Toledo, OH 43614, USA; Professor The University of Toledo, Department of Pediatrics, Toledo, OH, USA.

PMID: 31446299
DOI: 10.1016/j.jpba.2019.07.023

Abstract

This article describes the simultaneous determination of bedaquiline fumarate (TMC-207) and rifabutin in human plasma by stable isotope dilution tandem mass spectrometry. The methodology was developed for an investigation of potential drug-drug interactions of the two anti-tuberculosis drugs when given together to healthy human volunteers. Use of the two drugs in combination to treat disease caused by Mycobacterium tuberculosis is contemplated as the bacterium becomes resistant to many currently available drugs.

Keywords: 25-O-Desacetylrifabutin; Bedaquiline; Bedaquiline metabolite M2; Mycobacterium tuberculosis; Rifabutuin; Stable isotope dilution tandem mass spectrometry; TMC-207.

Publication types

Validation Study

MeSH terms

Antitubercular Agents / administration & dosage
Antitubercular Agents / blood*
Antitubercular Agents / pharmacokinetics
Chromatography, High Pressure Liquid / methods
Diarylquinolines / administration & dosage
Diarylquinolines / blood*
Diarylquinolines / pharmacokinetics
Drug Interactions
Drug Monitoring / methods*
Drug Therapy, Combination
Humans
Rifabutin / administration & dosage
Rifabutin / blood*
Rifabutin / pharmacokinetics
Tandem Mass Spectrometry / methods
Tuberculosis / drug therapy

Substances

Antitubercular Agents
Diarylquinolines
Rifabutin
bedaquiline