Study on pharmacokinetics of scopolamine hydrobromide gel transdermally administered in rats by microdialysis

Abstract

Objective: To establish and validate the HPLC-MS/MS method for the determination of scopolamine concentration in dermal microdialysis samples of rats,and study pharmacokinetics of scopolamine hydrobromide gel transdermally administered in rats.Methods: Scopolamine was separated with an Agilent Zorbax Extend C18 column.The mobile phase consisted of methanol-2 mmol/L ammonium formate(25∶75,the pH was adjusted to 3.5 by formic acid) at a flow rate of 0.3 ml/min and the column temperature was 40 ℃.The HPLC-MS/MS system was operated in the mode of multiple reaction monitoring with the electrospray ionization technique in positive mode.Results:Scopolamine was optimized at the transitions m/z 138.1-304.2.Calibration curve of scopolamine was linear within the range of 5.0-1 000 ng/ml.The inter day and intra day precision and accuracy were all less than 15%.Scopolamine could rapidly penetrate the skin and be absorbed.One hundred and fifty min after administration,the concentration of scopolamine reached peak,then dropped and maintained at a relatively high concentration range.The subcutaneous scopolamine concentration was decreased rapidly 9 h later.Conclusion:This method is sensitive and selective,and could be used to determine the concentration of scopolamine in the dermal microdialysis samples of the rats.