LAUSR

&NA; The aim of the present study was to develop a new marker for correcting water flux in the in situ single‐pass intestinal perfusion (SPIP) model. The new marker was designed and synthesized based on the application of both polyethylene glycol‐4000 (PEG‐4000) and phenol red as non‐absorbable markers. The new marker mPEG‐PR was obtained by combining phenol red with polyethylene glycol monomethyl ether‐4000 (mPEG‐4000) and verified by nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, gel permeability chromatograph (GPC) and differential scanning calorimetry (DSC). mPEG‐PR fully took the advantages of phenol red and PEG including the low permeability and the simple measuring method which were assessed by the in vitro and the in situ models. In the everted gut sac (EGS) studies, the permeability of mPEG‐PR was significantly reduced by nearly 4 times compared with phenol red, and the absorptive percentage of mPEG‐PR was <0.1% in 105 min. In addition, the solution with verapamil or without Ca2+ could help improve the absorption of phenol red but did not influence the absorption of mPEG‐PR. The results of isosorbide dinitrate as a model drug in the in situ SPIP study showed that both the mPEG‐PR marker and the gravimetric method were useful for correcting water flux, which had smaller coefficients of variation than the phenol red marker and the non‐corrected method. In conclusion, mPEG‐PR could potentially be applied as an accurate and convenient marker for correcting water volume in the intestinal perfusion study.