Toxicokinetic Study of a Gastroprotective Dose of Capsaicin by HPLC-FLD Method

Abstract

Background: A low dose of capsaicin and its natural homologs and analogs (capsaicinoids) have shown to prevent development of gastric mucosal damage of alcohol and non-steroid anti-inflammatory drugs. Based on this experimental observation, a drug development program has been initiated to develop per os applicable capsaicin containing drugs to eliminate gastrointestinal damage caused by non-steroid anti-inflammatory drugs. Methods: As a part of this program, a sensitive and selective reverse-phase high-performance liquid chromatography-based method with fluorescence detection has been developed for quantification of capsaicin and dihydrocapsaicin in experimental dog’s plasma. Results: The method was evaluated for a number of validation characteristics (selectivity, repeatability, and intermediate precision, LOD, LOQ, and calibration range). The limit of detection (LOD) was 2 ng/mL and the limit of quantification (LOQ) was 10 ng/mL for both capsaicin and dihydrocapsaicin. The method was used for analysis of capsaicin and dihydrocapsaicin in the plasma samples obtained after per os administration of low doses (0.1, 0.3, and 0.9 mg/kg bw) of Capsaicin Natural (USP 29) to the experimental animals. Conclusions: The obtained results indicated that the administered capsaicinoids did not reach the general circulation.

The Relative Importance of the Small Intestine and the Liver in Phase II Metabolic Transformations and Elimination of p-Nitrophenol Administered in Different Doses in the Rat

“…Formation of phenyl glucuronides and phenyl sulfates are generally considered to be detoxification processes [56]. As our present and previous results [22,23,29,30,34] demonstrate, the formed phenol conjugates can be reexcreted into the gastrointestinal system both by the liver and the small intestine. At the lower PNP concentrations (up to 500 µM), a higher fraction of the absorbed dose is reexcreted into the small intestine in the PNP-G form.…”

“…The selected doses ensure a lack of acute toxic effects in the investigated organs during the experiments. Furthermore, the therapeutic dose of several phenolic drugs (e.g., estrons [33], capsaicinoids [34]), and the monomer flavonoid content of individual foods [35], fall into the range of our selected concentrations. PNP, having a simple-almost exclusively glucuronide-and sulfate-forming-metabolic profile, seems to be a proper model compound to investigate the relative importance of these two phase II metabolic pathways in the set concentration range.…”

Effect of 3 Months-Feeding of a Powder Diet Fortified With Chilli (Guntur, Bird’s Eye, and Naga King) on Superoxide Dismutase Levels in Sd Rat

“…CAP's slow, sustained release has been correlated with anti-cancer activity [18], a preventive role in gastric cancer [19]. Interestingly, a toxicokinetic study showed that CAP dosed per oral route doesn't reach circulation; however, it prevents gastric damage and works like NSAID [41], which may become a suitable candidate for therapeutic use. It was also observed in an exploratory study on human subjects that ingestion of red chilli strongly affects gastric accommodation, which could be helpful in gastroesophageal reflux disease patients [42].…”

Dispersive magnetic solid-phase extraction for capsaicinoid compounds in human serum using LC-HRMS: targeted and non-targeted approaches

“…Several analytical techniques have been applied for the analysis of capsaicinoids, including gas chromatography [5] and liquid chromatography (LC), which has been by far the most widely preferred [6][7][8][9][10][11][12][13][14][15][16][17][18]. LC methods tend to use UV absorption spectrophotometry [6], fluorescence detection (FLD) [7][8][9], and mass spectrometry (MS) [10][11][12][13][14][15][16][17][18] as detection systems.…”