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Full-profile bioanalysis of polydisperse macromolecular hydroxyethyl starch 130/0.4 in rat plasma via LC-IS-CID coupled with MRM 认领 引用
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作者 Xin Xu Huan Yang +2 位作者 Jiachong Chi Xiangjun Meng Jingkai Gu 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第4期664-669,共6页
Hydroxyethyl starch 130/0.4(HES130/0.4)is a macromolecular polysaccharide with polydispersity,which is widely used as a plasma expander.Full-profile bioanalysis of HES130/0.4 is required to characterize its plasma pha... Hydroxyethyl starch 130/0.4(HES130/0.4)is a macromolecular polysaccharide with polydispersity,which is widely used as a plasma expander.Full-profile bioanalysis of HES130/0.4 is required to characterize its plasma pharmacokinetics,yet current analytical technologies struggle with this task due to its complex structure and composition.To address this existing lacuna within the realm of analytical science,we propose a liquid chromatography-electrospray ionization mass spectrometry(LC-ESI-MS)methodology for the full-profile bioanalysis of HES130/0.4.Amide column separation with gradient optimization eluted polydisperse HES130/0.4 as a single symmetric peak.In-source collision-induced dissociation(IS-CID)converted the numerous precursor ions of HES130/0.4 into a limited number of characteristic fragment ions,from which m/z 597.4 was selected as the"pseudo-precursor ion"for MRM quantification.The ion transition m/z 597.4→435.3 was identified as the quantitative ion pair.The method demonstrated a linear calibration curve from 40μg/mL to 4000μg/L,with accuracy and precision meeting acceptance criteria,confirming its reliability and reproducibility.Subsequently,the workflow was successfully applied to investigate the pharmacokinetics of HES130/0.4 in rat,revealing its large distribution volume and rapid elimination within 24 h.This work provides a straightforward approach for the full-profile quantification of HES130/0.4 in biological samples,overcoming the limitations of traditional methods in terms of poor specificity,low sensitivity and narrow linear range,and providing a reference for the in vivo full-profile bioanalysis of HES130/0.4 and other polysaccharides. 展开更多
关键词 HES130/0.4 Direct quantification Full-profile bioanalysis Pharmacokinetics IS-CID
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Full-profile pharmacokinetics, anticancer activity and toxicity of an extended release trivalent PEGylated irinotecan prodrug 认领 引用 被引量：8
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作者 Shiwen Song Dong Sun +7 位作者 Hong Wang Jinliang Wang Huijing Yan Xuan Zhao John Paul Fawcett Xin Xu Deqi Cai Jingkai Gu 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第8期3444-3453,共10页
Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite,SN-38.Unfortunately,the limited utility of irinotecan is attributed to its pH-dependent stability,short half-life a... Irinotecan is an anticancer topoisomerase I inhibitor that acts as a prodrug of the active metabolite,SN-38.Unfortunately,the limited utility of irinotecan is attributed to its pH-dependent stability,short half-life and dose-limiting toxicity.To address this problem,a novel trivalent PEGylated prodrug(PEG-[Irinotecan]3)has been synthesized and its full-profile pharmacokinetics,antitumor activity and toxicity compared with those of irinotecan.The results show that after intravenous administration to rats,PEG-[Irinotecan]3 undergoes stepwise loss of irinotecan to form PEG-[Irinotecan]3-x(x=1,2)and PEG-[linker]during which time the released irinotecan undergoes conversion to SN-38.As compared with conventional irinotecan,PEG-[Irinotecan]3 displays extended release of irinotecan and efficient formation of SN-38 with significantly improved AUC and half-life.In a colorectal cancer-bearing model in nude mice,the tumor concentrations of irinotecan and SN-38 produced by PEG-[Irinotecan]3 were respectively 86.2 and 2293 times higher at 48 h than produced by irinotecan.In summary,PEG-[Irinotecan]3 displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan.This supports the view that PEG-[Irinotecan]3 is a superior anticancer drug to irinotecan and it has entered the phaseⅡtrial stage. 展开更多
关键词 Irinotecan SN-38 Trivalent PEGylated irinotecan Prodrug Full-profile pharmacokinetics
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