A Novel UPLC-MS/MS Method for the Determination of Salvianolic Acid A in Rat Urine, Feces, and Bile and its Application to Excretion Study

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Author(s): Jialin Sun, Wen Xu , Junke Song , Xiao Li , Qie Guo, Wei Sun , Bing Han , Guanhua Du, Fanbo Jing*.

Journal Name: Current Pharmaceutical Analysis

Abstract:

Background: Salvianolic acid A (SAA) is a polyphenolic acid extracted from Salvia miltiorrhiza Bunge. It showed protective effect against diabetic complications after oral administration with a low bioavailability of 1.42%. Attempts have been made to develop it into a new medication. Intracorporal process of SAA is indistinct and no report regarding the excretion is available. Our preliminary experiment revealed that previous reported methods were unsuitable for the excretion study due to the serious matrix effect.

Methods: To better clarify its pharmacokinetics and avoid the interference of complex endogenous substances, a sensitive UPLC-MS/MS method with a better resolution was developed for the excretion study of SAA for the first time. The analytes were separated by reversed-phase chromatography with acetonitrile–water (containing 0.1% formic acid) gradient elution. The mass spectrometer was operated in the negative ESI mode and multiple reaction monitoring mode.

Results: This method was linear over the concentration range of 2.5-100, 5-100 and 5-100 ng/mL in urine, feces and bile, respectively. The accuracy, precision, stability, recovery and matrix effect were satisfactory in all matrices examined. The validated method was successfully applied to an excretion study in rats. After oral administration of 20 mg/kg, the average accumulated excretion amount of SAA in urine, feces and bile were 99.80, 32046.30 and 161.03 ng, respectively.

Conclusion: A quick but low elimination was observed. The date is useful for the clinical trial design of SAA.

Keywords: Salvianolic acid A, UPLC-MS/MS, rat, excretion, sensitivity, resolution

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(E-pub Ahead of Print)
DOI: 10.2174/1573412914666171211160018

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