title: Online solid phase extraction and liquid chromatography-mass spectrometric determination of nucleoside drugs in plasma.
abstract: The bioanalysis and especially the sample preparation of nucleoside drugs in complex media, such as human plasma, has been challenging due to the high polarity and high solubility of these drugs in water. Online solid phase extraction (SPE) offers significant advantages, such as automation and timesaving. Thus, several types of SPE columns have been developed for compounds with different polarities. In this study, SPE was applied to overcome the issue of sample pretreatment of nucleoside drugs in human plasma, with the final aim of establishing a robust analytical platform for drugs with similar structures. A simple, easy-to-use, and efficient method is described for the simultaneous determination of lamivudine, zidovudine, didanosine and emtricitabine in human plasma via online SPE and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Following a simple centrifugation step, a 10μL plasma sample was injected directly onto the HPLC system. The Oasis MCX cartridge was washed, and the analytes were removed by back-flushing directly onto the analytical column. The analytes were quantified using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. Similarly, with the development and application of a Bond Elut phenylboronic acid (PBA) SPE cartridge, a fully automated online SPE-HPLC-MS/MS method was established for the simultaneous determination of ribavirin and taribavirin in human plasma. Linear calibration curves were obtained over the range of 0.5-2000ngmL-1, and the limit of quantification ranged from 0.5ngmL-1to 10ngmL-1, which is sensitive enough for clinical drug monitoring. The intra- and inter-day precisions were in the range of 0.2-8.9%, and the trueness ranged between 88.9% and 113.1%. Excellent recoveries from plasma were achieved with a range between 86.7% and 105.1%. This procedure is easier to perform and requires less sample handling compared to methods previously described in the literature. This high-throughput method involving the direct injection of plasma samples may provide a practical solution for the analysis of multiple nucleoside drugs in clinical research. The method was tested in plasma samples from some patients and showed good performance.
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors: Man
authors: M
authors: Wang
authors: Infectious Disease Department, Tianjin Second People's Hospital, Tianjin 300071, PR China.
authors: Ping
authors: P
authors: Ma
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors: Xiaonan
authors: X
authors: Xi
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors: Lei
authors: L
authors: Liu
authors: College of Life Science, Nankai University, Tianjin 300071, PR China.
authors: Yabin
authors: Y
authors: Wen
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors: Kangning
authors: K
authors: Liu
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors: Liang
authors: L
authors: Sun
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China. Electronic address: yaxinlu@nankai.edu.cn.
authors: Yaxin
authors: Y
authors: Lu
authors: College of Pharmacy & State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China. Electronic address: zheng_yin@nankai.edu.cn.
authors: Zheng
authors: Z
authors: Yin
mesh_terms: D002853:Chromatography, Liquid; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000097:blood; D008795:Metronidazole / Q000097:blood; D009705:Nucleosides / Q000097:blood*; D009862:Online Systems; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D009705:Nucleosides; D008795:Metronidazole; D007294:Inositol; C102817:voglibose
keywords: Bioanalysis; Nucleoside drugs; Online SPE-LC-MS/MS