Pharmacokinetic Study Of The Active Ingredient And Compatibility Of Binaotong Nasal Spray

Binaotong nasal spray is obtained by extracting Ligusticum chuanxiong, borneoland musk, etc. It has the effect of promoting blood circulation to remove blood stasisand alleviating pain, which is used to treat migraine. In this work, Ligustrazine ischosen as the index component of compound traditional Chinese medicine, andpharmacokinetics of Ligustrazine is studied.Ligustrazine was determined by HPLC with reversed chromatographic columnand UV absorbance detector. The calibration curves for Ligustrazine in preparationwere linear in the range of2.638-26.379μg/mL. Regression equation for thecalibration curve of Ligustrazine was y=9814.2x+1329.6, r=0.9997. The totalconcentration of Ligustrazine in preparation was55.968μg/mL. The accuracy ofLigustrazine was96.42%, the R.S.D. of precision, reproducibility and stability test ofLigustrazine were within2%. The detection limit was2.558μg/mL and the limit ofquantification (LOQ) was0.293μg/mLIn pharmacokinetic study, coumarin is used as internal standard and samplepreparation is carried out by extraction and precipitation with methanol.Thecalibration curves for Ligustrazine in plasma were linear in the range of0.1112-16.68μg/mL. Representive regression equations for the calibration curve of Ligustrazinewas y=0.1729x+0.0052, r=0.9999. The accuracy of Ligustrazine was between98.83%-104.19%. The intra-day and inter-day precisions (R.S.D.) of Ligustrazinewere within2%, and extraction recoveries was91.22%-98.91%. The R.S.D. ofreproducibility and stability test of Ligustrazine are within5%. The detection limitwas55.6ng/mL and the limit of quantification was11.12ng/mL.Pharmacokinetics of Ligustrazine was studied after intranasal administered10,20and40mg/kg of Ligustrazine and intravenous administered5mg/kg ofLigustrazine. The pharmacokinetic parameters were fitted by DAS3.1.4pharmacokinetics program. The main parameters of Low, medium, high dose groupand intravenous injection group were as follows: Cmaxis8.08±1.7,16.54±1.18,3.12±2.56and62.57±2.50μg/mL, respectively. AUC(0-t)is228.93±15.64,399.27±31.82,728.92±39.35and1025.32±129.61mg/L*min, separately. CmaxandAUC(0-t)of three doses were increased with the increase of the drug dosage. Pharmacokinetics of Ligustrazine was studied with borneol and musk. CmaxofLigustrazine group, ligustrazine plus borneol group, ligustrazine plus syntheticborneol and musk group was18.97±1.55,21.69±2.39,22.95±2.54μg/mL, respectively.AUC(0-t)of three group was417.95±48.52,485.47±62.44,561.51±56.11mg/L*min,separately. Relative bioavailability of ligustrazine plus borneol group, ligustrazineplus borneol and musk group was116.15%,134.35%with ligustrazine group forreference. Cmaxof ligustrazine was increased and the relative bioavailability wasimproved, and results showed that absorption of ligustrazine was promoted aftercompatibility administration of borneol and musk.