Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence of ionization type, sample preparation, and biofluid

American Chemical Society (ACS) - Tập 14 - Trang 1290-1294 - 2003
Riet Dams1, Marilyn A. Huestis1, Willy E. Lambert2, Constance M. Murphy3
1Chemistry and Drug Metabolism, National Institute on Drug Abuse, National Institutes of Health, Baltimore, USA
2Laboratory of Toxicology, Ghent University, Ghent, Belgium
3Chemistry and Drug Metabolism, Clinical Pharmacology and Therapeutics, National Institute on Drug Abuse, National Institutes of Health, Baltimore, USA

Tóm tắt

The purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-µg/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS.

Tài liệu tham khảo

Krstulovic, A. M.; Lee, C. R.; Firmin, S.; Jacquet, G.; Van Dau, C. N.; Tessier, D. Applications of LC-MS Methodology in the Development of Pharmaceuticals. Lc Gc Europe 2002, 15, 31. Simal-Gandara, J.; Damant, A. P.; Castle, L. The Use of LC-MS in Studies of Migration from Food Contact Materials: A Review of Present Applications and Future Possibilities. Crit. Rev. Anal. Chem. 2002, 32, 47–78. Marquet, P. Progress of Liquid Chromatography-Mass Spectrometry in Clinical and Forensic Toxicology. Therapeut. Drug Monit. 2002, 24, 255–276. Thomas, R. Recent developments in LC-MS-MS for the Identification and Measurement of Nanoscale Amounts of Proteins and Peptides. Spectroscopy 2001, 16, 28. Hogendoorn, E.; van Zoonen, P. Recent and Future Developments of Liquid Chromatography in Pesticide Trace Analysis. J. Chromatogr. A 2000, 892, 435–453. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization—Principles and Practice. Mass Spectrom. Rev. 1990, 9, 37–70. Bruins, A. P. Mechanistic Aspects of Electrospray Ionization. J. Chromatogr. A 1998, 794, 345–357. Thomson, B. A.; Danylewychmay, L.; Henion, J. D. LC MS MS with an Atmospheric-Pressure Chemical Ionization Source. Am. Chem. Soc. 1983, 186, 19 (abstracts). Buhrman, D. L.; Price, P. I.; Rudewicz, P. J. Quantitation of SR 27417 in Human Plasma Using Electrospray Lquid Chromatography Tandem Mass Spectrometry: A Study of Ion Suppression. J. Am. Soc. Mass Spectrom. 1996, 7, 1099–1105. King, R.; Bonfiglio, R.; Fernandez-Metzler, C.; Miller-Stein, C.; Olah, T. Mechanistic Investigation of Ionization Suppression in Electrospray Ionization. J. Am. Soc. Mass Spectrom. 2000, 11, 942–950. Fu, I.; Woolf, E. J.; Matuszewski, B. K. Effect of the Sample Matrix on the Determination of Indinavir in Human Urine by HPLC with Turbo Ion Spray Tandem Mass Spectrometric Detection. J. Pharmaceut. Biomed. Anal. 1998, 18, 347–357. King, R.; Barrish, A.; Bonfiglio, R.; McLoughlin, D.; Merkle, K.; Miller-Stein, C.; Olah, T. Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics; Orlando, FL, 1998 Mei, H.; Hsieh, Y.; Nardo, C.; Xu, X.; Wang, S.; Ng, N.; Korfmacher, W. A. Investigation of Matrix Effects in Bioanalytical High-Performance Liquid Chromatography/Tandem Mass Spectrometric Assays: Application to Drug Discovery. Rapid Commun. Mass Spectrom. 2003, 17, 97–103. Cone, E. J.; Hillsgrove, M.; Darwin, W. D. Simultaneous Measurement of Cocaine, Cocaethylene, Their Metabolites, and Crack Pyrolysis Products by Gas-Chromatography Mass-Spectrometry. Clin. Chem. 1994, 40, 1299–1305. Bonfiglio, R.; King, R. C.; Olah, T. V.; Merkle, K. The Effects of Sample Preparation Methods on the Variability of the Electrospray Ionization Response for Model Drug Compounds. Rapid Commun. Mass Spectrom. 1999, 13, 1175–1185. Dams, R.; Murphy, C. M.; Choo, R. E.; Lambert, W. E.; De Leenheer, A. P.; Huestis, M. A. LC-APCI-MS/MS Analysis of Multiple Illicit Drugs, Methadone, and Their Metabolites in Oral Fluid Following Protein Precipitation. Anal. Chem. 2003, 75, 798–804. Smeraglia, J.; Baldrey, S. F.; Watson, D. Matrix Effects and Selectivity Issues in LC-MS-MS. Chromatographia 2002, 55, S95-S99. Hsieh, Y. S.; Chintala, M.; Mei, H.; Agans, J.; Brisson, J. M.; Ng, K.; Korfmacher, W. A. Quantitative Screening and Matrix Effect Studies of Drug Discovery Compounds in Monkey Plasma Using Fast-Gradient Liquid Chromatography/Tandem Mass Spectrometry. Rapid Commun. Mass Spectrom. 2001, 15, 2481–2487. Kebarle, P.; Tang, L. From Ions in Solution to Ions in the Gas-Phase—the Mechanism of Electrospray Mass-Spectrometry. Anal. Chem. 1993, 65, A972-A986.