-
Something wrong with this record ?
High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites
M Holcapek, L Kolarova, M Nobilis
Language English Country Germany
Document type Review
NLK
ProQuest Central
from 2005-01-01 to 2008-12-31
Medline Complete (EBSCOhost)
from 2003-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2005-01-01 to 2008-12-31
- MeSH
- Biotransformation MeSH
- Financing, Organized MeSH
- Pharmaceutical Preparations analysis chemistry metabolism MeSH
- Molecular Structure MeSH
- Tandem Mass Spectrometry MeSH
- Chromatography, High Pressure Liquid MeSH
- Xenobiotics analysis chemistry metabolism MeSH
- Publication type
- Review MeSH
Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002-2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H](+) and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H](-) ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MS( n ) analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well.
- 000
- 04245naa 2200349 a 4500
- 001
- bmc11003629
- 003
- CZ-PrNML
- 005
- 20111210202352.0
- 008
- 110302s2008 gw e eng||
- 009
- AR
- 040 __
- $a ABA008 $b cze $c ABA008 $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a gw
- 100 1_
- $a Holčapek, Michal, $d 1971- $7 ola2002159192
- 245 10
- $a High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites / $c M Holcapek, L Kolarova, M Nobilis
- 314 __
- $a Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Nam. Cs. Legii 565, 53210, Pardubice, Czech Republic. michal.holcapek@upce.cz
- 520 9_
- $a Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002-2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H](+) and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H](-) ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MS( n ) analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well.
- 650 _2
- $a biotransformace $7 D001711
- 650 _2
- $a vysokoúčinná kapalinová chromatografie $7 D002851
- 650 _2
- $a molekulární struktura $7 D015394
- 650 _2
- $a léčivé přípravky $x analýza $x chemie $x metabolismus $7 D004364
- 650 _2
- $a tandemová hmotnostní spektrometrie $7 D053719
- 650 _2
- $a xenobiotika $x analýza $x chemie $x metabolismus $7 D015262
- 650 _2
- $a financování organizované $7 D005381
- 655 _2
- $a přehledy $7 D016454
- 700 1_
- $a Kolářová, Lenka, $d 1975- $7 xx0076210
- 700 1_
- $a Nobilis, Milan $7 xx0079581
- 773 0_
- $t Analytical & Bioanalytical Chemistry $w MED00006638 $g Roč. 391, č. 1 (2008), s. 59-78
- 910 __
- $a ABA008 $b x $y 7
- 990 __
- $a 20110413120750 $b ABA008
- 991 __
- $a 20110413120750 $b ABA008
- 999 __
- $a ok $b bmc $g 831053 $s 695649
- BAS __
- $a 3
- BMC __
- $a 2008 $b 391 $c 1 $d 59-78 $m Analytical and bioanalytical chemistry $n Anal Bioanal Chem $x MED00006638
- LZP __
- $a 2011-3B/vtme