PMID- 29105858
OWN - NLM
STAT- MEDLINE
DCOM- 20180910
LR  - 20180910
IS  - 1097-0231 (Electronic)
IS  - 0951-4198 (Linking)
VI  - 32
IP  - 3
DP  - 2018 Feb 15
TI  - Investigation of metabolic profile of pimavanserin in rats by 
      ultrahigh-performance liquid chromatography combined with Fourier transform ion 
      cyclotron resonance mass spectrometry.
PG  - 269-276
LID - 10.1002/rcm.8025 [doi]
AB  - RATIONALE: Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a 
      promising candidate for treating Parkinson's disease psychosis. Our previous 
      study revealed that there might be the presence of extensive metabolites of 
      pimavanserin in rats. However, the metabolic fate of pimavanserin in vivo remains 
      unknown. Thus, it is essential to develop an efficient method to investigate the 
      metabolic profile of pimavanserin in rats. Fourier transform ion cyclotron 
      resonance mass spectrometry (FT-ICR-MS) to date has the highest mass measurement 
      accuracy and resolution of any mass spectrometry platform. METHODS: After a 
      single intragastric administration of pimavanserin at a dose of 50 mg kg(-1) , 
      plasma, bile, urine and feces were collected from rats. A novel and efficient 
      strategy was developed to analyze the metabolic profile of pimavanserin in vivo 
      based on ultrahigh-performance liquid chromatography (UHPLC) coupled with 
      FT-ICR-MS. RESULTS: A total of 23 metabolites were detected and tentatively 
      identified through comparing their mass spectrometry profiles with those of 
      pimavanserin. These metabolites were found in feces (22), bile (21), rat urine 
      (16) and plasma (15). Results demonstrated that metabolic pathways of 
      pimavanserin in rats included dehydrogenation, demethylation, deethylation, 
      depropylation, debutylation, hydroxylation, dihydroxylation and trihydroxylation. 
      CONCLUSIONS: A total of 22 phase I metabolites of pimavanserin were detected and 
      tentatively identified. This report presents the first study of screening and 
      identification of the metabolites of pimavanserin. The UHPLC/FT-ICR-MS method is 
      a powerful tool for exploring and identifying metabolites in complex biological 
      samples.
CI  - Copyright (c) 2017 John Wiley & Sons, Ltd.
FAU - Wu, Wenying
AU  - Wu W
AD  - School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
FAU - Chu, Yanjie
AU  - Chu Y
AD  - School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 
      Shenyang, 110016, China.
FAU - Wang, Shixiao
AU  - Wang S
AD  - School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
FAU - Sun, Xiaoyang
AU  - Sun X
AD  - School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
FAU - Zhang, Jingjing
AU  - Zhang J
AD  - School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
FAU - Wang, Yannian
AU  - Wang Y
AD  - School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 
      Shenyang, 110016, China.
FAU - Chen, Xiaohui
AU  - Chen X
AUID- ORCID: 0000-0002-5551-4282
AD  - School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Rapid Commun Mass Spectrom
JT  - Rapid communications in mass spectrometry : RCM
JID - 8802365
RN  - 0 (Piperidines)
RN  - 8W8T17847W (Urea)
RN  - JZ963P0DIK (pimavanserin)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Bile/chemistry
MH  - Chromatography, High Pressure Liquid/*methods
MH  - Feces
MH  - Fourier Analysis
MH  - Male
MH  - Mass Spectrometry/*methods
MH  - Piperidines/administration & dosage/metabolism/*pharmacokinetics
MH  - Rats, Sprague-Dawley
MH  - Tissue Distribution
MH  - Urea/administration & dosage/*analogs & derivatives/metabolism/pharmacokinetics
EDAT- 2017/11/07 06:00
MHDA- 2018/09/11 06:00
CRDT- 2017/11/07 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2017/10/23 00:00 [revised]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2017/11/07 06:00 [pubmed]
PHST- 2018/09/11 06:00 [medline]
PHST- 2017/11/07 06:00 [entrez]
AID - 10.1002/rcm.8025 [doi]
PST - ppublish
SO  - Rapid Commun Mass Spectrom. 2018 Feb 15;32(3):269-276. doi: 10.1002/rcm.8025.