PMID- 35443692
OWN - NLM
STAT- MEDLINE
DCOM- 20220422
LR  - 20220716
IS  - 1746-6148 (Electronic)
IS  - 1746-6148 (Linking)
VI  - 18
IP  - 1
DP  - 2022 Apr 20
TI  - Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC-MS/MS.
PG  - 145
LID - 10.1186/s12917-022-03245-0 [doi]
LID - 145
AB  - 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 x 50 mm, 3.5 mum) 
      at 30  degrees 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 muL. A good linear response was 
      obtained in a concentration range of 5-5000 ng.mL(-1) (r(2) = 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.
CI  - (c) 2022. The Author(s).
FAU - Zeng, Qingyuan
AU  - Zeng Q
AD  - Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, China.
AD  - Ningbo University School of Medicine, Ningbo University, Ningbo, China.
FAU - Si, Hongfei
AU  - Si H
AD  - College of Pharmacy, Jinan University, Guangzhou, China.
FAU - Lv, Kun
AU  - Lv K
AD  - Ningbo University School of Business, Ningbo University, Ningbo, China.
FAU - Mo, Jiao
AU  - Mo J
AD  - Ningbo University School of Medicine, Ningbo University, Ningbo, China.
FAU - Wang, Xinnian
AU  - Wang X
AD  - Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, China.
FAU - Yan, Biqing
AU  - Yan B
AD  - Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, China.
FAU - Zhang, Jili
AU  - Zhang J
AD  - Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo 
      University, Ningbo, China. zhangjili@nbu.edu.cn.
AD  - Ningbo University School of Medicine, Ningbo University, Ningbo, China. 
      zhangjili@nbu.edu.cn.
AD  - Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of 
      Agricultural Sciences, Lanzhou, 315211, China. zhangjili@nbu.edu.cn.
LA  - eng
GR  - (82102426)/National Natural Science Foundation of China/Youth Science Foundation 
      Project/
GR  - (LQ22H190001)/Zhejiang Natural Science Foundation/Youth Fund Project/
GR  - (SKLVEB2021KFKT007)/State Key Laboratory of Veterinary Etiological Biology Open 
      Fund/
GR  - (2021J103)/Ningbo Natural Science Foundation/
PT  - Journal Article
DEP - 20220420
PL  - England
TA  - BMC Vet Res
JT  - BMC veterinary research
JID - 101249759
RN  - 0 (Acrylates)
RN  - 56396-35-1 (2-cyano-3-(1-phenylindol-3-yl)acrylate)
SB  - IM
MH  - *Acrylates
MH  - Animals
MH  - Chromatography, High Pressure Liquid/methods/veterinary
MH  - Chromatography, Liquid/veterinary
MH  - Mice
MH  - *Tandem Mass Spectrometry/methods/veterinary
PMC - PMC9020015
OTO - NOTNLM
OT  - Glibenclamide
OT  - HPLC-MS/MS
OT  - Mouse plasma
OT  - Pharmacokinetics
OT  - UK-5099
COIS- The authors declare that they have no competing interests.
EDAT- 2022/04/22 06:00
MHDA- 2022/04/23 06:00
PMCR- 2022/04/20
CRDT- 2022/04/21 05:08
PHST- 2022/01/17 00:00 [received]
PHST- 2022/04/12 00:00 [accepted]
PHST- 2022/04/21 05:08 [entrez]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/04/23 06:00 [medline]
PHST- 2022/04/20 00:00 [pmc-release]
AID - 10.1186/s12917-022-03245-0 [pii]
AID - 3245 [pii]
AID - 10.1186/s12917-022-03245-0 [doi]
PST - epublish
SO  - BMC Vet Res. 2022 Apr 20;18(1):145. doi: 10.1186/s12917-022-03245-0.