title: Development and validation of LC-ESI-MS/MS method for analysis of moxifloxacin and levofloxacin in serum of multidrug-resistant tuberculosis patients: Potential application as therapeutic drug monitoring tool in medical diagnosis.
abstract: Moxifloxacin (MFX) and levofloxacin (LFX), class of fluoroquinolone antibiotics, are the two most prescribed drugs to multidrug resistant tuberculosis (MDR-TB) patients. A single, sensitive and reliable LC-ESI-MS/MS method was developed and validated to simultaneously quantitate the levels of these drugs in human serum where enrofloxacin (EFX) was used as internal standard (IS). Quantification was achieved by multiple reaction monitoring of selected mass transitions from precursor ions to product ions m/z 402.2→384.2 for MFX, 362.2→318.2 for LFX, and 362.1→318.3 for EFX. Calibration curves were plotted using concentrations ranging between 0.23-1000ng/mL for MFX and 0.13-1000ng/mL for LFX, and the correlation coefficients (r(2)) were in excess of 0.999. Intra- and inert-day accuracy was ranged between 92.1-104% with mean recoveries of 96% and 95.5% for MFX and LFX, respectively and precision was <9% at all quality control concentration levels. Matrix effect analysis showed extraction efficiency of 93.0-94.6% for MFX and 90.9-99.5% for LFX. Application of the developed method to real sample analysis resulted in efficient quantification of MFX and LFX in serum samples obtained from ten MDR-TB patients. The result indicated that the method could be applied as a potential drug monitoring tool to accurately analyze MFX and LFX within a short run time.
authors.affiliation: Research Institute of Life Science and Department of Chemistry, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Sung Joong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Research Institute of Life Science and Department of Chemistry, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Kebede Taye
authors.initials: KT
authors.lastname: Desta
authors.affiliation: International Tuberculosis Research Center, Changwon, Republic of Korea.
authors.forename: Seok Yong
authors.initials: SY
authors.lastname: Eum
authors.affiliation: Public Health Research Institute, University of medicine and Dentistry of NJ, Newark, NJ, USA.
authors.forename: Veronique
authors.initials: V
authors.lastname: Dartois
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Central Instrument Facility, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Bae
authors.affiliation: Research Institute of Life Science and Department of Chemistry, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: sshin@gnu.ac.kr.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
mesh_terms: D000995:Antitubercular Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D024841:Fluoroquinolones / Q000097:blood*; D006801:Humans; D064704:Levofloxacin / Q000097:blood*; D057230:Limit of Detection; D000077266:Moxifloxacin; D053719:Tandem Mass Spectrometry / Q000379:methods*; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D064704:Levofloxacin; D000077266:Moxifloxacin
keywords: LC–MS/MS; Levofloxacin; Moxifloxacin; Multi-drug resistant tuberculosis; Real sample analysis; Serum