title: The metal-organic framework MIL-101(Cr) as efficient adsorbent in a vortex-assisted dispersive solid-phase extraction of imatinib mesylate in rat plasma coupled with ultra-performance liquid chromatography/mass spectrometry: Application to a pharmacokinetic study.
abstract: Metal-organic framework MIL-101(Cr) was successfully used as an efficient sorbent in a vortex-assisted dispersive solid-phase extraction (VA-DSPE) and applied for the determination and the pharmacokinetic of imatinib mesylate in rat plasma by UPLC-MS/MS. In the enrichment of imatinib from rat plasma, the analyte was efficiently adsorbed on MIL-101(Cr) and simply recovered by using initial mobile phase (0.1% formic acid-methanol (6:4 v/v)) as elution solvent. Meanwhile, the protein in the plasma samples was excluded from the porous structure of MIL-101(Cr), leading to direct extraction of drug molecule from protein-rich biological samples without any other pretreatment procedure. After being removed, the supernatant was filtered and directly injected into the UPLC-MS/MS for the analysis of the target. The experimental parameters, including nature of MOFs, amount of MIL-101(Cr), pH value of aqueous solution, extraction time, type and volume of elution solvent, were systematically optimized. After VA-DSPE, chromatographic separation was performed on an ACQUITY UPLC(®) BEH C18 column (2.1mm×100mm, 1.7μm) with a 3min gradient elution using 0.1% formic acid and methanol as mobile phase at a flow rate of 0.3mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the positive ionization mode. The lower limit of quantification of 1ng/mL was achieved and the mean recovery of the analyte was higher than 81.2%. Moreover, computational simulation was primarily applied to predict the adsorption behavior and revealed the molecular interactions and free binding energies between MIL-101(Cr) and imatinib with the molecular modeling method, providing certain explanation of the adsorption mechanism. The originally established pretreatment and detection method has some merits, such as less solvent consumption, easy operation, higher sensitivity and lower matrix effect. And the MIL-101(Cr) exhibited a potential as an efficient sorbent in the enrichment of the analyte from complex biosamples.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Xiuna
authors.initials: X
authors.lastname: Jia
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, PR China. Electronic address: houxiaohong_syphu@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Hou
mesh_terms: D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002857:Chromium; D056831:Coordination Complexes / Q000737:chemistry*; D000068877:Imatinib Mesylate / Q000097:blood / Q000302:isolation & purification*; D008297:Male; D000073396:Metal-Organic Frameworks; D017207:Rats, Sprague-Dawley; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; C000589635:MIL-101; D000073396:Metal-Organic Frameworks; D002857:Chromium; D000068877:Imatinib Mesylate
keywords: Computational simulation; Dispersive solid-phase extraction; Imatinib mesylate; MIL-101(Cr); Pharmacokinetic