Spinosin is the major effective single constituent in the traditional Chinese herb Semen Ziziphi Spinosae, which is used for sedation and
hypnosis. For the further use of
spinosin in treating
insomnia, the pharmacokinetics and tissue distribution of
spinosin after
intravenous administration to rats was investigated. An HPLC method with an ODS column (250 mm x 4.6 mm, i.d.) and a mobile phase of
acetonitrile-water-
acetic acid (23:77:1) was used for the determination of
spinosin in the plasma and tissues of rats.
Vanillin was used as an internal standard, and
spinosin was detected at 334 nm. The calibration curve of
spinosin in plasma showed good linearity over the concentration range of 1-300 microg/ml, and the quantitation of limit of plasma was 1 microg/ml. The linear range of concentrations of
spinosin in the heart, spleen, stomach, lung, testis, brain, and intestine was 0.1-40 microg/ml and the quantitation limit was 0.1 microg/ml. The linear range of concentrations of
spinosin in the liver and kidney was 1-150 microg/ml, and the quantitation limit was 1 microg/ml. The correlation coefficients of all calibration curves were between 0.9939 and 0.9980. The intra and interrun precision for all samples was less than < or =11.0%. The time-concentration curve of
spinosin after the
intravenous administration of a single dose of 20 mg/kg to rats corresponded to the two-compartment model. The main pharmacokinetic parameters T(0.5alpha), T(0.5beta), CLs, AUC(0-T), and V(c) were 6.66 min, 51.5 min, 1.42 l.min(-1), 2.83 mg.min.ml(-1), and 14.0 l.kg(-1), respectively. At 20 min, a concentration peak occurred in liver and brain tissues. The highest level of
spinosin occurred in the liver, followed by the spleen and kidney. The lowest level of
spinosin appeared in the testis, followed by the brain.
Spinosin was not detected in smooth and skeletal muscle. After
intravenous administration, the
drug was distributed extensively and transferred quickly in rats in vivo.