Plasma persistence of 2-aminothiazoline-4-carboxylic acid in rat system determined by liquid chromatography tandem mass spectrometry

Abstract

2-Aminothiazoline-4-carboxylic acid (ATCA) was intravenously injected to rats in order to investigate its plasma distribution. ATCA was extracted from plasma samples by solid phase extraction (SPE) and molecularly imprinted polymer stir bar sorption extraction (MIP-SBSE). Detection and quantification of ATCA were achieved by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). It was found that the intravenously injected ATCA concentration quickly decreased to half within 2.5h in the rat system. However, after 2.5 h, the concentration of ATCA in plasma stayed constant at least 5 folds above the endogenous ATCA level for more then 48 h. This finding can be used for evaluating ATCA's diagnostic and forensic value as a biomarker for cyanide exposure.

Toxicokinetic profiles of α-ketoglutarate cyanohydrin, a cyanide detoxification product, following exposure to potassium cyanide

“…Although this study did not address the in vivo generation of ATCA from cyanide exposure, it is one of the first studies to address the distribution and elimination of ATCA. The plasma ATCA ranged from 0.96 to 18.5 M, and showed a consistent 5-fold increase over endogenous concentrations between 2.5 and 48 h post-exposure (Petrikovics et al, 2012). These findings suggest that the use of ATCA as a biomarker is promising, but further evaluation of the toxicokinetics of ATCA following cyanide exposure should be undertaken.…”

“…Evaluation of the toxicokinetic behavior of cyanide and its breakdown products provides insight into the best marker for verification of cyanide exposure. Such studies have been conducted for cyanide (Dirikolu et al, 2003;Leuschner et al, 1991;Sousa et al, 2003) and its major detoxification products, thiocyanate (Leuschner et al, 1991;Sousa et al, 2003) and ATCA (Petrikovics et al, 2012), in various animal models. The results of these studies are presented in Table 1.…”

“…The results of this study suggest that about 65-75% of absorbed cyanide is converted to thiocyanate, which is in close agreement with the 80% predicted by Ansell and Lewis (1970). Petrikovics et al (2012) studied the toxicokinetics of ATCA in rats following intravenous (IV) injection of ATCA at 100 mg/kg body weight. Although this study did not address the in vivo generation of ATCA from cyanide exposure, it is one of the first studies to address the distribution and elimination of ATCA.…”

Liquid-Chromatographic Methods for Carboxylic Acids in Biological Samples

“…We found that BCAT1 plays a significant role in the development of chronic myeloid leukemia [67]. In addition, disorders of α-keto acid levels in biological fluids are related to diseases such as diabetes mellitus, maple syrup urine disease, and ketoacidosis [68,69]. Therefore, the analysis of α-keto acids is attracting increasing interest.…”

“…SPE offered adequate precision of 5.9% RSD, but interferences derived from whole blood were detected near the ATCA peak. On the other hand, MIP-SBSE produced a single peak derived from ATCA, but the capacity was insufficient and the method suffered from low recoveries [69]. Lulinski et al synthesized a novel imprinted material in a dispersive SPE, providing a rapid (35 min for extraction) and low-cost clean-up technique [70].…”