PMID- 34545636
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 1097-0231 (Electronic)
IS  - 0951-4198 (Linking)
VI  - 35
IP  - 23
DP  - 2021
TI  - Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug 
      quantitation, metabolite detection, and distribution in tissue.
PG  - e9202
LID - 10.1002/rcm.9202 [doi]
AB  - RATIONALE: Spatially resolved and accurate quantitation of drug-related compounds 
      in tissue is a much-needed capability in drug discovery research. Here, 
      application of an integrated laser ablation-dropletProbe-mass spectrometry 
      surface sampling system (LADP-MS) is reported, which achieved absolute 
      quantitation of propranolol measured from <500 x 500 mum thin tissue samples. 
      METHODS: Mouse liver and kidney thin tissue sections were coated with parylene C 
      and analyzed for propranolol by a laser ablation/liquid extraction workflow. 
      Non-coated adjacent sections were microdissected for validation and processed 
      using standard bulk tissue extraction protocols. High-performance liquid 
      chromatography with positive ion mode electrospray ionization tandem mass 
      spectrometry was applied to detect the drug and its metabolites. RESULTS: 
      Absolute propranolol concentration in ~500 x 500 mum tissue regions measured by 
      the two methods agreed within +/-8% and had a relative standard deviation within 
      +/-17%. Quantitation down to ~400 x 400 mum tissue regions was shown, and this 
      resolution was also used for automated mapping of propranolol and phase II 
      hydroxypropranolol glucuronide metabolites in kidney tissue. CONCLUSIONS: This 
      study exemplifies the capabilities of integrated laser ablation-dropletProbe-mass 
      spectrometry (LADP-MS) for high resolution absolute drug quantitation analysis of 
      thin tissue sections. This capability will be valuable for applications needing 
      to quantitatively understand the spatial distribution of small molecules in 
      tissue.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Kertesz, Vilmos
AU  - Kertesz V
AUID- ORCID: 0000-0003-0186-5797
AD  - Bioanalytical Mass Spectrometry Group, Biosciences Division, Oak Ridge National 
      Laboratory, Oak Ridge, Tennessee, USA.
FAU - Cahill, John F
AU  - Cahill JF
AUID- ORCID: 0000-0002-9866-4010
AD  - Bioanalytical Mass Spectrometry Group, Biosciences Division, Oak Ridge National 
      Laboratory, Oak Ridge, Tennessee, USA.
FAU - Srijanto, Bernadeta R
AU  - Srijanto BR
AUID- ORCID: 0000-0002-1188-1267
AD  - Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak 
      Ridge, Tennessee, USA.
FAU - Collier, Charles P
AU  - Collier CP
AUID- ORCID: 0000-0002-8198-793X
AD  - Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak 
      Ridge, Tennessee, USA.
FAU - Vavrek, Marissa
AU  - Vavrek M
AUID- ORCID: 0000-0003-0240-2583
AD  - Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & 
      Co., Inc., Kenilworth, New Jersey, USA.
FAU - Chen, Bingming
AU  - Chen B
AUID- ORCID: 0000-0003-3573-4541
AD  - Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & 
      Co., Inc., Kenilworth, New Jersey, USA.
LA  - eng
GR  - Technology Transfer Maturation Program of Oak Ridge National Laboratory/
GR  - Bioimaging Science Program/
GR  - Biological and Environmental Research/
GR  - Office of Science/
GR  - U.S. Department of Energy (Office of Science, Office of Basic Energy Sciences and 
      Energy Efficiency and Renewable Energy, Solar Energy Technology Program)/
PT  - Journal Article
PL  - England
TA  - Rapid Commun Mass Spectrom
JT  - Rapid communications in mass spectrometry : RCM
JID - 8802365
RN  - 0 (Pharmaceutical Preparations)
RN  - 9Y8NXQ24VQ (Propranolol)
SB  - IM
MH  - Animals
MH  - Chromatography, High Pressure Liquid/methods
MH  - Equipment Design
MH  - Kidney/chemistry/diagnostic imaging
MH  - Lasers
MH  - Liver/chemistry/diagnostic imaging
MH  - Male
MH  - Mice
MH  - Molecular Imaging/*methods
MH  - *Pharmaceutical Preparations/analysis/metabolism
MH  - Propranolol/analysis/pharmacokinetics
MH  - Spectrometry, Mass, Electrospray Ionization/*methods
MH  - Tissue Distribution
EDAT- 2021/09/22 06:00
MHDA- 2022/02/01 06:00
CRDT- 2021/09/21 06:47
PHST- 2021/09/17 00:00 [revised]
PHST- 2021/08/12 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/09/21 06:47 [entrez]
AID - 10.1002/rcm.9202 [doi]
PST - ppublish
SO  - Rapid Commun Mass Spectrom. 2021;35(23):e9202. doi: 10.1002/rcm.9202.