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

Qingyuan Zeng; Hongfei Si; Kun Lv; Jiao Mo; Xinnian Wang; Biqing Yan; Jili Zhang

doi:10.1186/s12917-022-03245-0

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

BMC Vet Res. 2022 Apr 20;18(1):145. doi: 10.1186/s12917-022-03245-0.

Authors

Qingyuan Zeng^#^{1

2}, Hongfei Si^#³, Kun Lv⁴, Jiao Mo², Xinnian Wang¹, Biqing Yan¹, Jili Zhang^{5

6

7}

Affiliations

¹ Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.
² Ningbo University School of Medicine, Ningbo University, Ningbo, China.
³ College of Pharmacy, Jinan University, Guangzhou, China.
⁴ Ningbo University School of Business, Ningbo University, Ningbo, China.
⁵ Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China. zhangjili@nbu.edu.cn.
⁶ Ningbo University School of Medicine, Ningbo University, Ningbo, China. zhangjili@nbu.edu.cn.
⁷ Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 315211, China. zhangjili@nbu.edu.cn.

^# Contributed equally.

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 AUC_0-t was 42,103 ± 12,072 ng·h·mL^-1 and the MRT_0-t was 0.857 ± 0.143 h. The peak concentration (C_max) was 82,500 ± 20,745 ng·h·mL^-1, which occurred at a peak time (T_max) = 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.

Keywords: Glibenclamide; HPLC–MS/MS; Mouse plasma; Pharmacokinetics; UK-5099.

MeSH terms

Acrylates*
Animals
Chromatography, High Pressure Liquid / methods
Chromatography, High Pressure Liquid / veterinary
Chromatography, Liquid / veterinary
Mice
Tandem Mass Spectrometry* / methods
Tandem Mass Spectrometry* / veterinary

Substances

Acrylates
2-cyano-3-(1-phenylindol-3-yl)acrylate

Abstract

MeSH terms

Substances

Grants and funding