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OBJECTIVE To develop and validate for the simultaneous determination of four Sudan dyes (Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and SudanⅣ) in rat plasma for the first time, based on the ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method coupled with solidphase extraction (SPE) procedure in order to reduce the complex matrix interferences and enrich the analytes.METHODS 30 rats were randomly assigned to five groups (blank edible oil group, Sudan Ⅰ group, Sudan Ⅱ group, Sudan Ⅲ group, and SudanⅣ group) with six rats (3 males and 3 females)each.Sudan dyes (Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and SudanⅣ) were separately dissolved in 10 mg·ml-1 edible oil and administered via a single oral (po) dose of 50.0 mg·kg-1 to Sprague-Dawley (SD) rats.Approximately 20.0 μl of the rat blood sample (at 10.0, 20.0, 30.0, and 40.0 min and 1.0, 1.5,2.0, 3.0, 5.0, 7.0, 10.0, 15.0 and 24.0 h post-dosing for Sudan Ⅰ and Sudan Ⅱ;whereas 1.0, 2.0,3.0, 4.0, 5.0, 6.0, 7.0, 9.0, 11.0, 15.0, 20.0, 32.0 and 48.0 h post-dosing for Sudan Ⅲ and Sudan Ⅳ) was collected immediately centrifuged and cleaned using Cleanert C18 mixed-mode polymeric sorbent.Quantification was performed by an electrospray ionization source in the positive multiple reaction monitoring mode using D5-Sudan Ⅰ as the internal standard compensated for any matrix effect variability,including extraction and ionization variations.RESULTS The pharmacokinetic results demonstrate that Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and SudanⅣ reached the maximum point in the plasma drug concentration of rats at about 0.6046, 1.362, 4.196 and 4.341 h after oral administration, respectively.The concentration decreased gradually with an elimination half-life (t1/2) of 0.8374, 1.8102, 2.3909 and 2.364 h for Sudan Ⅰ, Sudan Ⅱ, Sudan Ⅲ, and Sudan Ⅳ, respectively.The absorption rate constants (ka) of Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and SudanⅣ were 3.996, 1.393, 0.4368 and 0.4395 1/h, which were significantly greater than their elimination rate constants (ke) of 0.8277, 0.3829, 0.2899, and 0.29321/h, respectively.The four Sudan dyes were easily absorbed and quickly accessible to the loop body of the SD rats.The phenomenon of rapid absorption possibly involves the specific and lipophilic chemical properties of the four Sudan dyes.Given the double phospholipid compositions of the cell membrane of the rat, the lipophilic Sudan dyes successfully and rapidly accessed the organic body.These results were in accordance with the maximum blood concentrations achieved at 630.91, 696.26, 349.39 and 1304.61 μg· L-1 for Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and SudanⅣ, respectively.The areas under the concentration-time curve (AUC0-∞) of Sudan Ⅰ , Sudan Ⅱ, Sudan Ⅲ, and Sudan Ⅳ were 1150.03,2966.66, 2706.37 and 10 013.91 μg· h-1· L-1, which also indicated the high bioavailability of the four analytes.CONCLUSION The successful application of the UFLC-MS/MS method to the pharmacokinetic study of four Sudan dyes suggested its suitability and sufficiency for use in pharmacokinetic studies.