Comparative Study on Pharmacokinetics of Morphine Hydrochloride 24-Hour Sustained-Release Tablets and Its Commercial Products in Beagle Dogs
Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of morphine hydrochloride concentration in the plasma of Beagle dogs,and to compare the pharmacokinetic behavior and sustained-release characteristics of self-made morphine hydrochloride 24-hour sustained-release tablets with commercial products.Methods Protein was isolated by precipitation with acetonitrile with phosphate as an internal standard.The chromatographic column was ACE Phenol column(100 mm×2.1 mm,5 µm),the mobile phase was 0.1％formic acid aqueous solution-0.1％formic acid acetonitrile solution(gradient elution),the flow rate was 500 µL/min.The quantitation analysis was performed by electrospray ionization source under multiple-reaction monitoring mode at mass charge ratio(m/z)of 286.1-165.3 for morphine and m/z of 300.2-165.1 for codeine.A single and three-cycle cross administration of the morphine hydrochloride 24-hour sustained-release tablets and the two commercial products were given in Beagle dogs,and the morphine hydrochloride concentration in plasma was determined by the LC-MS/MS method.The relevant pharmacokinetic parameters were calculated by the Phoenix WinNonlin 7.0 software.Results The linear range of morphine was 5-2 000ng/mL(r = 0.998 4,n = 8).The RSD and RE of accuracy,precision,and stability test results were all lower than 20％.There was no significant difference in the area under the blood drug concentration-time curve(AUC0-t)and maximum blood drug concentration(Cmax)between self-made product and two commercial products(P>0.05).The peak time(tmax)of the self-made product was 13.9 times that of commercial product 1 and 7.1 times that of commercial product 2,respectively.Conclusion Self-made morphine hydrochloride 24-hour sustained-release tablets have more significant sustained-release characteristics than the two commercial products.
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