Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC‐MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration

Abstract

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

Effectiveness of Columbianadin, a Bioactive Coumarin Derivative, in Perturbing Transient and Persistent INa

“…The intestinal absorption and transportation of CBN has been previously reported [ 27 , 34 ]. This compound was noticed to be readily absorbed into blood stream and well distributed into various organs after intravenous or oral administration to rats [ 11 , 35 , 36 , 37 ]. Moreover, by use of liquid chromatography tandem mass spectrometry, the peak CBN level in rats following intravenous administration (5 mg/Kg) was previously measured to reach around 4.7 µg/mL (or 14 µM) [ 37 , 38 ].…”

“…This compound was noticed to be readily absorbed into blood stream and well distributed into various organs after intravenous or oral administration to rats [ 11 , 35 , 36 , 37 ]. Moreover, by use of liquid chromatography tandem mass spectrometry, the peak CBN level in rats following intravenous administration (5 mg/Kg) was previously measured to reach around 4.7 µg/mL (or 14 µM) [ 37 , 38 ]. This value is similar to effective IC 50 required for its inhibition of peak I Na presented herein; however, it is virtually higher than either that for block of late I Na or the K D value optimally estimated from the binding scheme.…”

Traditional Chinese Medicine of Angelicae Pubescentis Radix: A Review of Phytochemistry, Pharmacology and Pharmacokinetics

“…Oral administration of pure columbianadin (40) may be more beneficial for the clinical efficacy of columbianadin (40) (25 mg/kg) than APR extract (3.74 g/kg). Pure columbianadin (40) group: T max : 3.03 ± 1.87 h, C max : 1.82 ± 0.64 ng/ml, AUC (0-tn) : 1.05 ± 1.02 ng/ml/h; APR extract group: T max : 0.55 ± 0.33 h, C max : 13.33 ± 25.37 ng/ml, AUC (0-tn) : 28.80 ± 41.46 ng/ml/h (Li et al, 2018).…”

Comparison of Pharmacokinetic Profiles of 14 Major Bioactive Components in Normal and Arthritic Model Rats after Oral Administration of Angelicae pubescentis Radix by UPLC-MS/MS

“…Chang et al used the LC-MS/MS method to simultaneously determine scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthol, isoimperatorin of the AP extract in normal rat plasma [ 21 ]. Li et al used the LC-MS/MS method to simultaneously determine columbianadin and its metabolite columbianetin in rat plasm [ 23 ]. However, it is worth noting that there are no pharmacokinetic studies on phenolic acid compounds in AP.…”