Development of a simple and rapid UPLC-MS/MS method for determination of 8-deacetyl-yunaconitine in rat plasma and its application to pharmacokinetics.

In this paper, UPLC-MS/MS was used to determine 8-deacetyl-yunaconitine in the plasma of rats after oral and intravenous administration. Six rats were orally (po) administered 8-deacetyl-yunaconitine (5 mg/kg), while another six rats were intravenously (iv) administered the drug (0.1 mg/kg). A standard curve of known concentrations of 8-deacetyl-yunaconitine in rat plasma was generated over the range of 0.3-600 ng/mL. The intra-day and inter-day precision of 8-deacetyl-yunaconitine in rat plasma was lower than 15 %, while the accuracy ranged between 97.7 % and 105.5 %. In addition, the matrix effect ranged between 95.3 % and 105.6 %, while the recovery was greater than 82.8 %. This determined method was then applied in measuring the pharmacokinetics of 8-deacetyl-yunaconitine in rats. The AUC(0-t) values were 73.0 ± 24.6 and 1770.0 ± 530.6 ng/mL h for intravenous and oral administration, respectively, and the bioavailability was 48.5 %. The half-life (t1/2) was determined to be 4.5 ± 1.7 h and 3.2 ± 0.7 h for intravenous and oral administration, respectively, indicating that the metabolism of the xenobiotic was quick in the rats.

A Preliminary Research on the Efficacy and Toxicity of Yunaconitine and 8-deacetyl- yunaconitine Isolated from the Processed Products of Aconiti Knsnezoffii Radix / 中国中医药信息杂志

Objective To conduct comparative study on the analgesic and anti-inflammatory effects as well as the acute toxicity of yunaconitine and 8-deacetyl-yunaconitine isolated from the processed products of Aconiti Knsnezoffii Radix.Methods The methods of hot plate test and writhing test were used to evaluate the analgesic effect. Anti-inflammation action was observed by the models of auricle swelling caused by dimethylbenzene. LD50 was determined by the method of Bliss.Results Yunaconitine and 8-deacetyl-yunaconitine have analgesia effect on the pain caused by hot-plate, but there were no statistically significant difference. The pain caused by acetic acid had obvious analgesic action. High and low dose of yunaconitine could significantly reduce the number of mice body torsion and extend the incubation period of pain in mice. The effect of 8-deacetyl-yunaconitine was remarkable only in the high dose. Compared with solvent group, there were little differences in inhibiting effect of auricle swelling caused by dimethylbenzene, and anti-inflammatory action was not exact. The poisonousness of yunaconitine was nearly 20 times of 8-deacetyl-yunaconitine.Conclusion Yunaconitine and 8-deacetyl-yunaconitine may be the analgesic medicine for peripheral analgesic effect. The poisonousness of 8-deacetyl-yunaconitine is less than yunaconitine, the effect is remarkable to the pain caused by acetic acid, and the security is high.