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Background   Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts.Methods   A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L 1 , L 2 , and L 3  in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol.Results   The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen.Conclusion   These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L 1 , L 2 , and L 3  after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.

Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae