Detail
Article
Online article
FT
Medvik - BMC
  • 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

. 2008 ; 391 (1) : 59-78.

Language English Country Germany

Document type Review

E-resources

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

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

Find record