title: Determination of moxifloxacin in human plasma, plasma ultrafiltrate, and cerebrospinal fluid by a rapid and simple liquid chromatography- tandem mass spectrometry method.
abstract: Moxifloxacin (MFX) is a useful agent in the treatment of multi-drug-resistant tuberculosis (MDR-TB). At Tuberculosis Centre Beatrixoord, a referral center for tuberculosis in the Netherlands, approximately 36% of the patients have received MFX as treatment. Based on the variability of MFX AUC, the variability of in vitro susceptibility to MFX of M. tuberculosis, and the variability of penetration into sanctuary sites, measuring the concentration of MFX in plasma and cerebrospinal fluid (CSF) could be recommended. Therefore, a rapid and validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyzing method with a simple pretreatment procedure was developed for therapeutic drug monitoring of MFX in human plasma and CSF. Because of the potential influence of protein binding on efficacy, we decided to determine both bound and unbound (ultrafiltrate) fraction of MFX. The calibration curves were linear in the therapeutic range of 0.05 to 5.0 mg/L plasma and CSF with CV in the range of -5.4% to 9.3%. MFX ultrafiltrate samples could be determined with the same method setup for analysis of MFX in CSF. The LC-MS-MS method developed in this study is suitable for monitoring MFX in human plasma, plasma ultrafiltrate, and CSF.
authors.affiliation: Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arianna D
authors.initials: AD
authors.lastname: Pranger
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
authors.forename: A Mireille A
authors.initials: AM
authors.lastname: Wessels
authors.forename: Ben
authors.initials: B
authors.lastname: Greijdanus
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
mesh_terms: D000995:Antitubercular Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001372:Aza Compounds / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D024841:Fluoroquinolones; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000032:analysis; D000077266:Moxifloxacin; D011804:Quinolines / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014390:Tuberculosis, Meningeal / Q000188:drug therapy; D014462:Ultrafiltration
chemical_list: D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; C024316:cianopramine; D007099:Imipramine; D000077266:Moxifloxacin