Development and validation of an LC‐MS/MS method for the determination of tigecycline in human plasma and cerebrospinal fluid and its application to a pharmacokinetic study. (6th July 2016)

• Record Type: Journal Article
• Authors: Mei, Shenghui; Luo, Xuying; Li, Xingang; Li, Qian; Huo, Jiping; Yang, Li; Zhu, Leting; Feng, Weixing; Zhou, Jianxin; Shi, Guangzhi; Zhao, Zhigang
• Is Part Of: Biomedical chromatography. Volume 30:Number 12(2016:Dec.)
• Page Start: 1992
• Page End: 2002
• Publication Date: 2016-07-06
• Subjects: cerebrospinal fluid -- liquid chromatography with tandem mass spectrometry -- method development and validation -- plasma -- pharmacokinetic study -- tigecycline; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3776
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: Tigecycline (TGC) is an important antibiotic in treating various drug‐resistant bacteria. The dosage regimen for cerebral intraventricular TGC is still unknown. The aim of the study was to develop and validate liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methods for the determination of TGC in human plasma and cerebrospinal fluid (CSF) to obtain an applicable regimen. The ion transitions under ESI positive model were performed at m / z 586.3 > 513.2 and m / z 595.3 > 514.3 for TGC and d9‐TGC internal standard (IS). For plasma and CSF samples, the calibration curve of TGC was linear within the ranges 25–2000 and 250–100, 000 ng/mL; the IS normalized matrix effect was within the ranges 96.46–101.06% and 101.13–103.58%, respectively, for all. TGC was stable under all tested conditions. The patient received 1 mg intraventricular and 49 mg intravenous administration of TGC. The AUC0–12 in plasma and CSF calculated according to our noncompartment model were 4713 and 23, 0238 h ng/mL, respectively. Given our findings cerebral intraventricular TGC may be a choice for clinicians to treat drug‐resistant Gram‐negative bacterial‐induced meningitis and the safety and efficacy of this administration route warrants further study.