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

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• 作者：Shenghui Mei ; Xuying Luo ; Xingang Li ; Qian Li ; Jiping Huo ; Li Yang ; Leting Zhu ; Weixing Feng ; Jianxin Zhou ; Guangzhi Shi and Zhigang Zhao
• 刊名：Biomedical Chromatography
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：30
• 期：12
• 页码：1992-2002
• 全文大小：785K
• ISSN：1099-0801

文摘

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 AUC_0–12 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.