LC-MS/MS systematic toxicological analysis: Comparison of MS/MS spectra obtained with different instruments and settings

被引:70
作者
Jansen, R [1 ]
Lachatre, G [1 ]
Marquet, P [1 ]
机构
[1] Univ Hosp, Dept Pharmacol Toxicol, F-87042 Limoges, France
关键词
systematic toxicological analysis; LC-MS/MS; mass spectra library;
D O I
10.1016/j.clinbiochem.2004.11.003
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Objectives: To compare the mass spectra obtained using a linear-ion-trap (LIT) tandem mass spectrometer (QTRAP) operated in the "enhanced product ion scan" (EPI) mode with those obtained in the classical triple-quadrupole product ion scan (PIS) mode run on the same as well as on two other instruments (TSQ-Quantum and Quattro-Micro). Design and methods: After tentative standardization of ion fragmentation and transmission in both polarities using a reference compound (glafenine) on the three instruments, eight test compounds detected in the positive mode and five in the negative mode were systematically infused in different ionization Sources and spectral acquisition performed over approximately 5 s. The relative intensity of the ions present in the resulting spectra was quantitatively and statistically compared. Also, the intra-day and inter-day variabilities of these relative intensities, as well as the effect of increasing compound concentration, were studied using QTRAP operated in EPI mode. Results: The EPI and PIS modes operated on a single LIT MS/MS instrument resulted in significant differences in relative ion intensities in both polarities, and so did the other two instruments despite prior standardization with glafenine. Some fragments could be absent in certain spectra, but no unexpected or unique fragments showed up. Intra-day variability was smaller in the LIT EPI than in the regular PIS mode and in the positive than in the negative polarity. In EPI mode, both intra- and inter-day variabilities increased when the relative intensity decreased. The effect of increasing Concentration on the relative intensity of major and minor ions was small but significant in both polarities. Finally, contamination and cleansing of the ionization source also had noticeable effects on MS/MS spectra, though the cause is unclear. Conclusions: MS/MS spectra do not offer the expected inter-instrument reproducibility despite an attempt at standardizing the fragmentation conditions using a reference compound. However, although the inter-iitstrument differences in ion relative intensity were significant, the spectra obtained looked almost similar. This suggests that in library searching algorithms, higher weight should be assigned for the m/z ratios than for their relative intensity in the spectra. (c) 2004 The Canadian Society of Clinical Chemists. All rights reserved.
引用
收藏
页码:362 / 372
页数:11
相关论文
共 10 条
[1]  
Decaestecker TN, 2000, RAPID COMMUN MASS SP, V14, P1787, DOI 10.1002/1097-0231(20001015)14:19<1787::AID-RCM94>3.0.CO
[2]  
2-S
[3]  
Fitzgerald RL, 1999, CLIN CHEM, V45, P1224
[4]   Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique [J].
Marquet, P ;
Saint-Marcoux, F ;
Gamble, TN ;
Leblanc, JCY .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2003, 789 (01) :9-18
[5]   Is LC-MS suitable for a comprehensive screening of drugs and poisons in clinical toxicology? [J].
Marquet, P .
THERAPEUTIC DRUG MONITORING, 2002, 24 (01) :125-133
[6]   In-source CID mass spectral libraries for the "general unknown" screening of drugs and toxicants [J].
Marquet, P ;
Venisse, N ;
Lacassie, É ;
Lachâtre, G .
ANALUSIS, 2000, 28 (10) :925-934A
[7]  
RIVIER L, 37 TIAFT M 2001 AUG
[8]   Evaluation of an improved general unknown screening procedure using liquid-chromatography-electrospray-mass spectrometry by comparison with gas chromatography and high-performance liquid-chromatography-diode array detection [J].
Saint-Marcoux, F ;
Lachâtre, G ;
Marquet, P .
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, 2003, 14 (01) :14-22
[9]   A general unknown screening procedure for drugs and toxic compounds in serum using liquid chromatography-electrospray-single quadrupole mass spectrometry [J].
Venisse, N ;
Marquet, P ;
Duchoslav, E ;
Dupuy, JL ;
Lachâtre, G .
JOURNAL OF ANALYTICAL TOXICOLOGY, 2003, 27 (01) :7-14
[10]   Tune compounds for electrospray ionisation/in-source collision-induced dissociation with mass spectral library searching [J].
Weinmann, W ;
Stoertzel, M ;
Vogt, S ;
Wendt, J .
JOURNAL OF CHROMATOGRAPHY A, 2001, 926 (01) :199-209