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
基金supported by the National Natural Science Foundation of China(Nos.82030107,82304443,82373944)。
文摘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.
