Determination of the neuropharmacological drug nodakenin in rat plasma and brain tissues by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic studies

Abstract

A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0-1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were <15% in both biological media. This assay was successfully applied to plasma and brain pharmacokinetic studies of nodakenin in rats after intravenous administration.

Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study

“…UHPLC conditions including columns, column temperature, mobile phase system, and flow rate were investigated to optimize the sensitivity, retention time, and resolution. In previous literature, water/acetonitrile [ 13 , 14 , 16 , 21 , 23 ] or water/acetonitrile containing formic acid [ 15 , 18 , 19 ] was used as the mobile phase for the detection of coumarins. Therefore, we tested these two conditions.…”

“…However, its LLOQ value is at least four-times higher than that in our study. Other methods have shown lower sensitivity, with LLOQs ranging from 50 to 250 ng/mL for combined D and DA [ 13 , 14 , 17 ], 2 to 100 ng/mL for nodakenin [ 16 , 19 , 20 ], and 39 to 200 ng/mL for DOH [ 13 , 14 , 17 , 18 ]. In comparison, our simultaneous analytical method was the most sensitive, simple, and cost-effective for determining the four coumarins in plasma (LLOQ of 0.05 ng/mL for all components with the PP method using 0.1 mL plasma).…”

“…Despite these pharmacological activities, pharmacokinetic (PK) studies for major components of AGN are limited. Several PK studies of AGN in mice [ 13 ], rats [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and humans [ 23 ] have been published. Most of them have characterized PKs of one or two components of courmarins from extracted AGN or shown PKs of combined D and DA.…”

“…During the past few decades, many analytical methods using various quantitative analysis instruments—including HPLC-UV [ 13 , 14 , 15 , 16 , 17 , 20 ], LC-MS/MS [ 18 , 19 ], and UHPLC-MS/MS [ 23 ]—have been reported for coumarins from AGN root. Most of these publications have suggested analytical methods for one or two components of coumarins in rat plasma.…”

“…The highest sensitivity at LLOQ of 0.1–1 ng/mL for detecting D, DA, and DOH in human plasma has been reported by using UPLC-MS/MS with solid supported liquid extraction (SLE) [ 23 ]. Analytical techniques of nodakenin in rat plasma have been reported with LLOQ of 100 ng/mL [ 20 ] and 250 ng/mL [ 16 ] using HPLC-UV and 2 ng/mL using LC-MS/MS [ 19 ]. However, no study has reported simultaneous quantification of the four major components of AGN (i.e., D, DA, nodakenin, and DOH) in human plasma.…”