title: 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.
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 AUC0-12in 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.
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100045, People's Republic of China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Mei
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Xuying
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100045, People's Republic of China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Huo
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100045, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Leting
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, People's Republic of China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Feng
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100045, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008911:Minocycline / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline
keywords: cerebrospinal fluid; liquid chromatography with tandem mass spectrometry; method development and validation; pharmacokinetic study; plasma; tigecycline