Studies On Quality And Human Bioavailability Of Compound Tramadol Hydrochloride Sustained Release Tablet

It is a compound tramadol hydrochloride sustained release bilayer tablet, comprised of tramadol hydrochloride and acetaminophen. Established the quality standard after studying the description, idetification, related substances, dissolution and assay. It provides evidence on the stability of the compound thamadol thdrochloride sustained release bilayer tablet storage for18months. The test provides evidence for the determination of the drug production quality.Methods:It is detected by HPLC method for the dissolution, related substance and content assay. Chromatographic condition:C18column, mobile phase methanol--Acetate buffer solution (pH4.5)=(30:70)or(40:60),λ=271nm,The4-aminophenol p-aminophenol is detemined by colorimetric method. Dissolution test condition:basket-rack,100rpm,900ml,water.Results:The linear range of tramadol hydrochloride is2.8008～93.36ug/ml, The linear range of acetaminophen is14.6272～731.36ug/ml, in assay determination. The dissolution of tramadol hydrochloride and acetaminophen is30～50%、45～75%、55～80%、>75%in1h、2h、4h、10hour. This product is stable in light, heat and unstable in wet.It established an LC/MS/MS method to determine Tramadol hydrochloride plasma concentration, Diphenhydramine solution was used as the internal standard for40ng/ml. The plasma concentrations of acetaminophen was determined by HPLC.The main pharmacokinetic parameters of the product and the reference preparation are as follow:Tramadol hydrochloride Tmax(2.6±1.0和1.1±0.4h), Cmax(252±141,250±80ng/ml),The relative bioavailability of the average degree is112.3±55.8%; Acetaminophen Tmax (0.9±0.4,1.0±0.5h), Cmax(18.9±6.6,25.5±7.3ug/ml), The relative bioavailability of the average degree is97.6±22.8%。 Conclusion:The standard established could be used as a quality control of compound tramadol hydrochloride sustained release bilayer tablet. tested were found to be bioequivalent to reference preparat i on.