PMID- 29571134
OWN - NLM
STAT- MEDLINE
DCOM- 20180917
LR  - 20180917
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 154
DP  - 2018 May 30
TI  - Determination of oroxylin A and oroxylin A 7-O-d-glucuronide in HepG2 cell lysate 
      and subcellular fractions with SPE-UPLC-MS/MS: Cellular pharmacokinetic study to 
      indicate anti-cancer mechanisms.
PG  - 364-372
LID - S0731-7085(17)33062-5 [pii]
LID - 10.1016/j.jpba.2018.03.019 [doi]
AB  - Targeting therapy of anti-cancer drugs has been gaining increasing attention. 
      Cell pharmacokinetics have been used for in vitro disposition evaluation, as well 
      as drug-drug interaction for anti-cancer drugs, revealing their fate after 
      entering tumor. Flavonoid compound oroxylin A (OA) possesses strong anti-cancer 
      effects especially on the liver and breast cancer. However, despite the low 
      bioavailability, the disposition of OA and its active metabolite in the target 
      cancer cells remained unclear. In current study, a highly sensitive and selective 
      solid phase extraction (SPE)-UPLC-MS/MS method was developed and validated to 
      simultaneously quantify the concentrations of OA and its major active metabolite 
      oroxylin A 7-O-d-glucuronide (OG) in HepG2 cell lysate and multiple subcellular 
      organelle fractions. The proposed method appeared to be suitable for the analysis 
      with desirable linearity(R(2) > 0.99). The relative standard deviations (RSDs) of 
      intra- and inter-assay precision and accuracy were less than 9.9% and -7.7%, 8.4% 
      and 11% for OA and OG in cell lysate respectively. The intra- precision and 
      accuracy was less than 9.5% and -11.3%, 9.4% and 12.3% for OA and OG in 
      subcellular organelles respectively. The range of absolute recovery of this 
      method in the cell lysate was from 73.1% +/- 1.4% to 87.9% +/- 6.7%. The RSDs of 
      matrix effects of the quality control (QC) samples were below 15%. The uptake and 
      distribution experiments demonstrated a time-dependent transport characteristic 
      in HepG2 cell lines. Furthermore, both OA and OG were mainly distributed into 
      nuclei after taken up by the tumor cells. In addition, OG was also distributed 
      into mitochondria, which indicates another potential target of OG. The present 
      study, for the first time, reports the in vitro cell pharmacokinetics profiles of 
      OA and OG in tumor cell lines in vitro.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, 
      China; Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, 
      Nanjing, Jiangsu Province, 211198, China.
FAU - Cong, Danhua
AU  - Cong D
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - An, Dongchen
AU  - An D
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Fan, Ali
AU  - Fan A
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Liu, Qi
AU  - Liu Q
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Yi, Yingyue
AU  - Yi Y
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Song, Zhongjin
AU  - Song Z
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Chen, Xijing
AU  - Chen X
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Lu, Yang
AU  - Lu Y
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China.
FAU - Zhao, Di
AU  - Zhao D
AD  - Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing, 
      Jiangsu Province, 211198, China. Electronic address: zhaodihehe@126.com.
FAU - He, Ling
AU  - He L
AD  - Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, 
      China. Electronic address: heling92@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20180311
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Flavones)
RN  - 0 (Flavonoids)
RN  - 0 (Glucuronides)
RN  - 0 (oroxylin A-7-O-glucuronide)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
SB  - IM
MH  - Antineoplastic Agents/*pharmacokinetics
MH  - Biological Availability
MH  - Cell Line, Tumor
MH  - Chromatography, High Pressure Liquid/methods
MH  - Drug Interactions
MH  - Flavones/*pharmacokinetics
MH  - Flavonoids/*pharmacokinetics
MH  - Glucuronides/*pharmacokinetics
MH  - Hep G2 Cells
MH  - Humans
MH  - Mitochondria/metabolism
MH  - Reproducibility of Results
MH  - Solid Phase Extraction/methods
MH  - Subcellular Fractions/metabolism
MH  - Tandem Mass Spectrometry/methods
OTO - NOTNLM
OT  - Cell pharmacokinetics
OT  - Oroxylin A
OT  - Oroxylin A 7-O-d-glucuronide
OT  - SPE-UPLC-MS/MS
OT  - Subcellular distribution
EDAT- 2018/03/24 06:00
MHDA- 2018/09/18 06:00
CRDT- 2018/03/24 06:00
PHST- 2017/12/13 00:00 [received]
PHST- 2018/03/07 00:00 [revised]
PHST- 2018/03/10 00:00 [accepted]
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2018/09/18 06:00 [medline]
PHST- 2018/03/24 06:00 [entrez]
AID - S0731-7085(17)33062-5 [pii]
AID - 10.1016/j.jpba.2018.03.019 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2018 May 30;154:364-372. doi: 10.1016/j.jpba.2018.03.019. 
      Epub 2018 Mar 11.