Aralia mandshrica is a well-known traditional Chinese medicine from Northeast China commonly used to treat digestive, circulatory and immune system disorders. Calenduloside E is one of its bioactive components currently under evaluation as a pure drug. In this study, a highly sensitive and rapid method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of calenduloside E and its active metabolite oleanolic acid in beagle dog plasma has been developed and validated. Samples containing the ammonium salt of simvastatin acid as internal standard (IS) were purified by solid phase extraction and separated on a SUPELCO Ascentis-C-18 column (50 mm x 4.6 mm i.d., 5 mu m) using gradient elution with 0.35% formic acid and acetonitrile. Analytes and IS were detected in a cycle time of 5 min after ionization in the negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 631.4 -> 455.4 and m/z 435.4 -> 319.0 for calenduloside E and IS respectively and by single ion monitoring of the ion at m/z 455.4 for oleanolic acid. The method was linear over the concentration range 0.4-100 ng/mL for both analytes using 0.5 mL plasma. Inter-and intra-day precisions were both <6.96% with accuracies <6.40%. In the pharmacokinetic (PK) study, beagle dogs were given oral doses of calenduloside E (1.05, 2.10 and 4.20 mg/kg) and an intravenous injection of 2.10 mg/kg. The absolute bioavailability of calenduloside E was only 0.58%. Area under the plasma concentration time curve (AUC(((0-t))) for the oral doses of calenduloside E was approximately dose proportional while other PK parameters (t(1/2), T-max and MRT) showed no significant differences among the three doses (P>0.05). The PK data provide a useful platform on which to base future clinical studies of calenduloside E. (C) 2014 Elsevier B.V. All rights reserved.
[1]Jilin Univ, Coll Life Sci, Res Ctr Drug Metab, Changchun 130012, Peoples R China.
[2]Jilin Univ, Hosp 1, Res Inst Translat Med, Clin Pharmacol Ctr, Changchun 130061, Peoples R China.
[3]Jilin Univ, Sch Pharmaceut Sci, Changchun 130021, Peoples R China.
[4]Acad Chinese Med Sci Jilin Prov, Changchun 130021, Peoples R China.
[5]Univ Otago, Sch Pharm, Dunedin, New Zealand.
[6]Chinese Acad Med Sci, Beijing 100193, Peoples R China.
[7]Peking Union Med Coll, Beijing 100193, Peoples R China.
(8.0+极速模式)