Pharmacokinetics of compound huperzine a and ginkgolide b solid lipid nanospheres (SLN) after oral administration to beagle dogs / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics of solid lipid nanoparticles loaded with huperzine A and ginkgolide B in beagle dogs, and compare the pharmacokinetics and bioavailability with huperzine A commercial tablets. METHODS: The analytes and internal standard (diazepam and glibenclamide) were extracted from plasma by liquid-liquid extraction and analyzed on a C18 column. The mobile phase consisted of acetonitrile-methanol-10 mmol · L-1 ammonium acetate (304030, V/V/V, pH adjusted to 6-7 with formic acid) at a flow rate of 0.3 mL · min-1. The column temperature was 25℃. Electrospray ionization (ESI) source was applied. Huperzine A and diazepam were operated in positive mode. Ginkgolide B and glibenclamide were operated in negative mode. The precursor-product ion combinations of m/z 243.2→210.2, m/z 285.2→193.2, m/z 423.1→367.3, m/z 492.3→369.1 were used to quantify huperzine A, diazepam, ginkgolide B, and glibenclamide, respectively. Pharmacokinetic parameters were calculated by DAS2.0, and statistical analysis was done by SPSS19.0 software. RESULTS The main pharmacokinetic parameters of huperzine A in HA-GB-SLN and huperzine A commercial tablets were as follows t1/2 (4.59 ± 1.04) and (12.02 ± 0.98) h, ρmax(5.55 ± 0.97) and (2.04 ± 0.23) ng · mL-1, tmax(2.92 ± 0.37) and (8.33 ± 0.82) h, MRT (5.31 ± 0.35) and (16.13 ± 1.18) h, respectively. The relative bioavailability of HA-GB-SLN was (157.67 ± 4.85)%. The main pharmacokinetic parameters of ginkgolide B in HA-GB-SLN were as follows t1/2 (2.81 ± 0.35) h, ρmax (45.91 ± 2.89) ng · mL-1, tmax (1.58 ± 0.02) h, MRT (6.96 ± 0.33) h, AUC0-18(510.79 ± 17.77) ng · h · mL-1, AUC0-∞ (525.45 ± 16.68) ng · h · mL-1. CONCLUSION: The method is sensitive, accurate, specific, and convenient for the pharmacokinetic study of huperzine A. Compared with huperzine A commercial tablets, solid lipid nanoparticles loaded with huperzine A and ginkgolide B have better absorption, shorter onset time, and significantly improved bioavailability.