Background: The Phellodendri amurensis cortex is a traditional Chinese medicine with multiple pharmacodymic uses (antibacterial, anti-inflammation, antitumor, etc). It is often processed by saltwater to strengthen its effects in terms of nourishing yin to reduce pathogenic fire and reducing asthenic fever. To clarify the principle of saltwater processing, an experiment of pharmacokinetic comparison after oral administration from crude P. amurensis cortex and its saltwater processed product was carried out. Materials and Methods: A validated and sensitive ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) method was established for simultaneous quantification of five alkaloids and one triterpene in rat. An UPLC C18column was used for chromatograph separation by an elution program with the mobile phase consisting of 0.1% formic acid and acetonitrile. Each analytes and internal standard, nimodipine, was detected using positive ion scan mode via multiple reaction monitoring mode. All of the validation parameters investigated involving selectivity, precision, accuracy, extraction recovery, matrix effects, and stability shown this approach was suitable to the pharmacokinetic study. Results: Pharmacokinetic profiles showed these parameters of maximum of drug concentration and AUC0-tof alkaloids analytes elevated remarkably after oral administration of P. amurensis cortex processed with the saltwater. Conclusion: The results suggested that the absorption effect from the saltwater processed product was better than those from crude product, which could explain that saltwater processing may enhance the activity of clearing heat and removing toxicity from P. amurensis cortex.