Pharmacokinetic study comparing pure desoxo-narchinol A and nardosinonediol with extracts from Nardostachys jatamansi

Abstract

Nardostachyos Radix et Rhizoma (NR) is a valuable medicinal herb widely used in Korea, India, and China for the treatment of many diseases. Desoxo-narchinol A (DA) and nardosinonediol (ND) are the two main bioactive compounds belonging to the sesquiterpene group. Desoxo-narchinol A possesses anti-inflammatory activity while ND exhibits anti-depressant and cardioprotective activities. A pharmacokinetic study is important to decide whether the isolated compounds or the NR extract have better pharmacological activity. Hence, we developed an analytical method for studying the pharmacokinetics of DA and ND after oral administration of the pure compounds and herbal extract. An optimized liquid chromatography-mass spectrometry method (LC-MS/MS) with solid-phase extraction (SPE) for sample preparation was developed. A ZORBAX Extend C18 column (2.1 × 50 mm, 3.5 μm) was used under gradient elution with acetonitrile and 0.1% formic acid in water as the mobile phase. Validation experiments assessing accuracy, precision, and stability were satisfactory; the lower limit of quantification was 5 ng/mL. For the pharmacokinetic study, three groups of rats were administrated pure DA, pure ND, or NR extract orally. Concentrations of DA and ND in their plasma were determined by the developed method. Pharmacokinetic parameters, including the time to achieve maximum plasma concentration (T_max) and the area under the plasma concentration curve from time zero to infinity (AUC_0-∞), were compared for the herbal extract and pure compounds. The T_max of the pure compound and the NR extract for DA was 7.50 and 8.33 min, respectively, compared to 5.00 and 5.83 min for the pure compound and the NR extract for ND, respectively. The AUC_0-∞ of the pure compound and the NR extract for DA was 156.34 and 133.90 μg min/mL, respectively, and that for the NR extract for ND was 6.42 and 4.15 μg min/mL, respectively. LC-MS/MS was used to determine DA and ND in rat plasma. The pharmacokinetic profile of each pure compound and those in the extract were characterized and compared.

Keywords: Desoxo-narchinol A; LC-MS/MS; Nardosinonediol; Nardostachyos Radix et Rhizomas; Pharmacokinetic study.