Determination of closantel enantiomers in black goat plasma and their pharmacokinetic characteristics

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Nov 1:1210:123414. doi: 10.1016/j.jchromb.2022.123414. Epub 2022 Aug 9.

Abstract

Closantel is a broad-spectrum antiparasitic drug widely used in livestock. It is a chiral drug consisting of a pair of enantiomers. An accurate, selective, and validated method was established for separating and detecting closantel enantiomers in black goat plasma. Separation of enantiomers was achieved in Chiralpak AD-3 based on amylose tris (3,5-dimethyl phenyl carbamates) under a gradient mobile phase composed of n-hexane-TFA (100:0.1, v/v) and IPA-MeOH-TFA (99:1:0.1, v/v/v). Mean recoveries of the two enantiomers at three spiking levels ranged from 97.4 % to 102.0 % with a relative standard deviation ≤ 4.5 %. The limit of quantification was 1.35 µg/mL for each enantiomer in plasma. The proposed method was successfully applied to investigate the enantioselective pharmacokinetics of closantel enantiomers (E1 and E2) in black goats following an intramuscular closantel sodium at 5 mg/kg b.w. The results revealed that peak plasma concentration and area under the curve were significantly different between the two enantiomers (p < 0.05). Cmax and AUC0-∞ for closantel E1 were approximately 3 times greater than closantel E2. These findings would help in further evaluation of pharmacokinetic, pharmacodynamic, and toxicity of the individual enantiomers of closantel in food animals.

Keywords: Black goats; Closantel; Enantioselective; High-performance liquid chromatography; Pharmacokinetics.

MeSH terms

  • Amylose*
  • Animals
  • Antiparasitic Agents
  • Chromatography, High Pressure Liquid / methods
  • Goats*
  • Phenylcarbamates
  • Reproducibility of Results
  • Salicylanilides
  • Sodium
  • Stereoisomerism

Substances

  • Antiparasitic Agents
  • Phenylcarbamates
  • Salicylanilides
  • Amylose
  • Sodium
  • closantel