Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC–MS/MS

Abstract

Background UK-5099 is a potent mitochondrial acetone carrier inhibitor, that exhibits anticancer activity. Recently, the anti-Toxoplasma gondii activity of UK-5099 was proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effect of UK-5099. Methods and results A simple and fast high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) analysis method was established and verified in terms of its linearity, matrix effect, accuracy, precision, recovery and stability. The analytes were separated by an Agilent ZORBAX XDB-C18 column (2.1 × 50 mm, 3.5 μm) at 30 °C. A gradient mobile phase consisting of water with 0.1% formic acid (FA) (phase A) and acetonitrile (ACN) (phase B) was delivered at a flow rate of 0.40 mL·min−1 with an injection volume of 5 μL. A good linear response was obtained in a concentration range of 5–5000 ng·mL−1 (r2 = 0.9947). The lower limit of quantification (LLOQ) was 5 ng·mL−1. The extraction recovery of UK-5099 was greater than 95%. The inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) of less than 15%. This method has been successfully applied to the pharmacokinetic evaluation of UK-5099 in mouse plasma. In health mice, the main pharmacokinetic parameters of UK-5099 after intraperitoneal administration were measured using a noncompartmental model, in which the AUC0-t was 42,103 ± 12,072 ng·h·mL−1 and the MRT0-t was 0.857 ± 0.143 h. The peak concentration (Cmax) was 82,500 ± 20,745 ng·h·mL−1, which occurred at a peak time (Tmax) = 0.250 ± 0.000 h. Conclusions A fast and sensitive HPLC–MS/MS method was developed, validated and successfully used for the determination of UK-5099 levels in mice after intraperitoneal administration. This study was the first report of the pharmacokinetic parameters of UK-5099 in mice, which will help to further study the administration of UK-5099 in animals and humans.

Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo

“…The optimal pharmacokinetic model was determined according to the minimum Akaike Information Criterion (AIC) value and used for data fitting and parameter estimation. The peak plasma concentration (C max ), area under the plasma curve (AUC), half-life (T 1/2 ) and peak time (T max ) were expressed as the mean ± SD ( Zeng et al, 2022 ).…”