Metabolite profiling in rat urine by liquid chromatography/electrospray ion trap mass spectrometry. Application to the study of heavy metal toxicity

被引:77
作者
Lafaye, A
Junot, C
Ramounet-Le Gall, B
Fritsch, P
Tabet, JC
Ezan, E
机构
[1] Univ Paris 06, CNRS, Lab Chim Struct Organ & Biol, UMR 7613, F-75252 Paris 05, France
[2] CEA Saclay, DSV, DRM, Serv Pharmacol & Immunol, F-91191 Gif Sur Yvette, France
[3] CEA, SRCA, DRR, DSV,Lab Radiotoxicol, Bruyeres Le Chatel, France
关键词
D O I
10.1002/rcm.1243
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
This work reports the use of reverse-phase liquid chromatography coupled to electrospray ion trap (QIT) mass spectrometry for the analysis of the metabolome in rat urine. An injection of 20 muL of urine into the chromatographic system is followed by a slow gradient elution and mass spectrometric detection in the scanning mode from m/z 100-1000 in both positive and negative modes. Over a time scale of 90 min, 30 and 20 resolved peaks were observed in the positive and the negative modes, respectively, corresponding to the presence of a few hundred m/z ratios. By using a QIT analyzer, data-dependent tandem mass spectrometry of selected m/z ratios identified several compounds in rat urine and characterized various chemical families, including carboxylic acids, amines, sulfated compounds, glucuronides and glycosides, by the observation of characteristic fragment ions or neutral losses. The method has been applied to the investigation of the chronic toxicity of heavy metals in rat urine. A few tens of m/z ratios, differing in intensity more than threefold from control values, were observed in both positive and negative modes. The time variations for some selected ions suggest that LC/ESI-MS could allow selective characterization of biomarkers in response to specific toxic compounds. Copyright (C) 2003 John Wiley Sons, Ltd.
引用
收藏
页码:2541 / 2549
页数:9
相关论文
共 43 条
[1]  
Aharoni Asaph, 2002, OMICS A Journal of Integrative Biology, V6, P217, DOI 10.1089/15362310260256882
[2]   Direct measurement of steroid sulfate and glucuronide conjugates with high-performance liquid chromatography mass spectrometry [J].
Bowers, LD ;
Sanaullah .
JOURNAL OF CHROMATOGRAPHY B, 1996, 687 (01) :61-68
[3]   Electrospray ionization Fourier transform mass spectrometric analysis of wine [J].
Cooper, HJ ;
Marshall, AG .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2001, 49 (12) :5710-5718
[4]   Use of directly coupled ion-exchange liquid chromatography-mass spectrometry and liquid chromatography-nuclear magnetic resonance spectroscopy as a strategy for polar metabolite identification [J].
Dear, GJ ;
Plumb, RS ;
Sweatman, BC ;
Parry, PS ;
Roberts, AD ;
Lindon, JC ;
Nicholson, JK ;
Ismail, IM .
JOURNAL OF CHROMATOGRAPHY B, 2000, 748 (01) :295-309
[5]  
Dear GJ, 1999, RAPID COMMUN MASS SP, V13, P886, DOI 10.1002/(SICI)1097-0231(19990530)13:10<886::AID-RCM577>3.0.CO
[6]  
2-B
[7]   Identification and quantitative determination of 3-chloro-2-hydroxypropylmercapturic acid and alpha-chlorohydrin in urine of rats treated with epichlorohydrin [J].
DeRooij, BM ;
Commandeur, JNM ;
Ramcharan, JR ;
Schuilenburg, HCP ;
VanBaar, BLM ;
Vermeulen, NPE .
JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS, 1996, 685 (02) :241-250
[8]   Characterization of isoflavones and their conjugates in female rat urine using LC/MS/MS [J].
Fang, NB ;
Yu, SG ;
Badger, TM .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2002, 50 (09) :2700-2707
[9]   Identification of uncommon plant metabolites based on calculation of elemental compositions using gas chromatography and quadrupole mass spectrometry [J].
Fiehn, O ;
Kopka, J ;
Trethewey, RN ;
Willmitzer, L .
ANALYTICAL CHEMISTRY, 2000, 72 (15) :3573-3580
[10]   Metabolite profiling for plant functional genomics [J].
Fiehn, O ;
Kopka, J ;
Dörmann, P ;
Altmann, T ;
Trethewey, RN ;
Willmitzer, L .
NATURE BIOTECHNOLOGY, 2000, 18 (11) :1157-1161