High‐performance liquid chromatography method for determination of carnosic acid in rat plasma and its application to pharmacokinetic study

Abstract

A sensitive and reproducible high-performance liquid chromatography method with ultraviolet detection (UV) was developed for the determination of carnosic acid (CA) in rat plasma. After simple acidification and liquid-liquid extraction of plasma samples using gemfibrozil as an internal standard, the supernatant was evaporated to dryness under a gentle stream of nitrogen. The residue was reconstituted in 200 microL before being injected into the chromatographic system. The analysis was performed on a C(18) column protected by an ODS guard column using acetonitrile-0.1% phosphoric acid (55:45, v/v) as mobile phase, and the wavelength of the UV detector was set at 210 nm. The calibration curve was linear over the range of 0.265-265.0 microg/mL with a correlation coefficient of 0.9997. The recovery for plasma samples of 0.530, 13.25, 132.5 and 265.0 microg/mL was 72.2, 87.9, 90.4 and 94.7%, respectively. The intra-day and inter-day relative standard deviations for the measurements of quality control samples were less than 3.1%. The stability of the plasma samples was also validated. This method was successfully used to study the pharmacokinetics and bioavailability of CA in rats.

Absorption, Distribution and Elimination of Carnosic Acid, A Natural Antioxidant from Rosmarinus officinalis, in Rats

“…The time-plasma concentration profiles of the present study are in agreement with the results found by Yan et al [15] where an IV and intra gastric administration was given of 10 and 90 mg CA/kg, to 5 and 8 rats, respectively. We fitted the time-concentration profile of the IV administrated rats to a two phase exponential decay curve instead of a single exponential model in the latter study.…”

“…However, a slow absorption of CA after PO administrations was found with a T max of 136.6 min, meaning that CA retained in the blood for a long time. In agreement, Yan et al [15] described that the absorption of CA after intragastric administration was slow (T max of 125.6 min). Since the results from the IV experiment showed that CA is eliminated from the blood rapidly, desorption of CA is thought to be rather slow.…”

“…Following analysis of CA in rat plasma after intravenous and intragastric administration, Yan et al [15] reported a bioavailability of 65%. However, information on the deposition in various tissues and on the elimination is not readily available in the scientific literature.…”

In Vitro Hepatotoxicity and Cytochrome P450 Induction and Inhibition Characteristics of Carnosic Acid, a Dietary Supplement with Antiadipogenic Properties

“…Therefore, at concentrations used as a food additive, it is assumed that carnosic acid levels would not cause significant hepatotoxicity or DDI. However, at doses needed to elicit statistically significant weight loss and antiadipogenic effects in ob/ob mice (Wang et al, 2011), it is calculated that plasma concentrations in these animals would exceed 100 M based on the published pharmacokinetic parameters of carnosic acid in the rat (Yan et al, 2009;Doolaege et al, 2011). This concentration is equal to or greater than the carnosic acid concentrations used in the current human hepatocyte studies.…”

Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells

“…Carnosic acid concentration in rosemary ethanolic extract has been reported to be approximately 30 mg/gm fresh weight [40]. A pharmacokinetic study in SD rats revealed that CA is absorbed into the bloodstream after oral administration (90 mg/kg) with a high peak plasma concentration (*100 lM), which slowly declined with time remaining at the level of * 30 lM for at least 24 h [41]. Human clinical studies are yet to be carried out and therefore the bioavailability of CA in humans has not yet been established.…”