Establishment and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Tigecycline in Critically Ill Patients

Abstract

Utilizing tigecycline-d9 as an internal standard (IS), we establish and validate a simple, effective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative measurement of tigecycline (TGC) in patient plasma. Acetonitrile was used as a precipitant to process plasma samples by a protein precipitation method. The analyte and IS were separated on an HSS T3 (2.1 × 100 mm, 3.5 μm) chromatographic column using isocratic program with a mobile phase comprising of 80% solvent A (water containing 0.1% formic acid (v/v) with 5 mM ammonium acetate) and 20% solvent B (acetonitrile) with a flow rate of 0.3 mL/min. The mass spectrometer, scanning in multireaction monitoring (MRM) mode and using an electrospray ion source (ESI), operated in the positive-ion mode. The ion pairs used for quantitative analysis were m/z 586.4 ⟶ 513.3 and m/z 595.5 ⟶ 514.3 for TGC and the IS, respectively. The range of the linear calibration curve obtained with this approach was 50–5000 ng/ml. Intra- and interbatch precision for TGC quantitation were less than 7.2%, and the accuracy ranged from 93.4 to 101.8%. The IS-normalized matrix effect was 87 to 104%. Due to its high precision and accuracy, this novel method allows for fast quantitation of TGC with a total analysis time of 2 min. This approach was effectively applied to study the pharmacokinetics of TGC in critically ill adult patients.

Concurrent Determination of Tigecycline, Tetracyclines and Their 4-Epimer Derivatives in Chicken Muscle Isolated from a Reversed-Phase Chromatography System Using Tandem Mass Spectrometry

“…The experiment was carried out in accordance with the relevant regulations of the EU Commission Decision 2002/657/EC [ 39 ] and the U.S. Food and Drug Administration Bioanalytical Method Validation 05/24/18 [ 40 ]. As stated in the introduction, the sample objects for TGC determination are blood and tissue [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The method of simultaneously determining tetracyclines, including TGC, established in this study should not be compared with other determination studies involving TGC [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] in terms of sample preparation.…”

“…As stated in the introduction, the sample objects for TGC determination are blood and tissue [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The method of simultaneously determining tetracyclines, including TGC, established in this study should not be compared with other determination studies involving TGC [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] in terms of sample preparation. Since solvent extraction was operated as the extraction method of targets, this study is comparable with the study that used solvent extraction for sample preparation in the simultaneous detection method for tetracyclines in muscle (or meat), as ascertained in Table 1 .…”

“…Among the reported TGC detection methods [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], there is no method for the simultaneous determination of TGC and other tetracyclines in animal-derived foods. The analytes in this study included four tetracyclines (TC, CTC, OTC and DOXY), as specified in China’s current national food safety standards, coupled with their three 4-epimer derivatives (4-epi-TC, 4-epi-CTC and 4-epi-OTC) and the novel glycylcycline (TGC).…”

“…The reported methods for the determination of TGC include rapid turbidimetric assay [ 17 ], monoclonal antibody-based immunochromatography [ 18 ], liquid chromatography (LC) [ 19 , 20 , 21 , 22 , 23 , 24 ] and LC–tandem mass spectrometry (LC–MS/MS) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Two published works use LC–diode array detection (LC–DAD) as an LC method [ 19 , 20 ], and another four use LC–ultraviolet detection (LC–UVD) [ 21 , 22 , 23 , 24 ].…”

“…Two published works use LC–diode array detection (LC–DAD) as an LC method [ 19 , 20 ], and another four use LC–ultraviolet detection (LC–UVD) [ 21 , 22 , 23 , 24 ]. LC–MS/MS methods have been developed in various samples, including human serum [ 25 ], human plasma [ 26 , 27 , 28 ], turkey plasma [ 29 ], human plasma and cerebrospinal fluid [ 30 ], human bone [ 31 ], rat bone [ 32 ], human skin [ 33 ], human lung epithelial cells and polymorphonuclear neutrophils [ 34 ], human gall bladder, bile, colon, bone, synovial fluid, lung and cerebrospinal fluid [ 35 ], and rat brain tissues [ 36 ]. Overall, there is no research on the simultaneous detection of TGC and other tetracyclines in animal-derived foods using LC–MS/MS methods.…”