An exquisitively sensitive and specific analytical technique, mass spectroscopy, has traditionally been a valuable and often indispensible tool to the medicinal chemist. In the past, whilc conventional electron and chemical ionization (EI & CI) techniques have provided a means of both structure elucidation and quantitative analysis, especially in combination with gas chromatography (GC/MS), these applications have been limited to organic molecules which were sufficiently stable to undergo transtion to the vapor phase, such as drugs and their derivatized free metabolites. Unfortunately, this requirement restricted the utility of mass spectrometry to materials whose molecular weight did not exceed aout 1,500 Daltons and prevented the investigation of many of the molecular species which are of interest to the medicinal chemist and health scientist. However, recent developments in "soft" ionization and sample introduction techniques combined with the advancements in mass spectrometry instrumentation and computerization have greatly increased both the range of compounds and complexity of samples now amenable to mass spectrometric analysis. Atmospheric pressure ionization (API) techniques, such as electrospray (ES), have permitted the coupling of the liquid chromatrograph to the mass spectrometer (LC/MS) and allowed the analysis of high molecular weight (> 100,000 Daltons), nonvolitale and thermally labile biological substances at the femtomole level with a minimum of sample perturbation. These ionization and sample introduction methods in combination with tandem mass spectrometry (MS/MS) and the enhanced data collection and processing capabilities have brought a new dimension of problem solving to these disciplines.

 From the exploration of CIMS in the early 1970's to developments of methodologies utilizing ES/LC/MS and MS/MS in the present day, the graduate students and faculty of the Department have lead the way in the application of classical and new mass spectrometric techniques to problems associated with the understanding of the mechanisms of drug metabolism, interactions and disposition. The Department's commitment to the training of doctoral candidates is, perhaps, best exemplified by the establishment of the Mass Spectrometry Facility in 1981. The primary objective of the Facility, which has helped the Department to earn national and international recognition, is to assist graduate students and other investigators in utilizing both classical and new mass spectrometric techniques as analytical research tools. Unique aspects of the Facility include: (1) learning by a "hands-on" approach to mass spectrometry; (2) ready access to "state-of-the-art" high performance mass spectrometers; and (3) a highly visible experienced professional staff offering technical support and training. But perhaps the most prominent feature of the Facility and the Department, in general, lies in the pursuit of excellence and the spirit of collegiality.

Recent Publications

 P. G. Pearson, W. N. Howald and S. D. Nelson, "Screening Strategy for the Detection of Derivatized Glutathione Conjugates by Tandem Mass Spectrometry," Anal. Chem., 62, 1827-1836 (1990).

 C. C. Farnsworth, P. J. Casey, W. N. Howald, J. A. Glomset and M. H. Gelb, "Structural Characterization of Prenyl Groups Attached to Proteins," Methods: A Companion to Methods in Enzymology, 1, 231-240 (1990).

 H. K. Yamane, C. F. Farnsworth, H. Xie, T. Evans, W. N. Howald, M. H. Gelb, J. A. Glomset, S. Clarke and B. K.-K. Fung, "Membrane-binding Domain of the Small G Protein G25K Contains and S-(All-trans-Geranylgeranyl) cysteine Methyl Ester at its Carboxyl Terminus," Proc. Nat. Acad. Sci., USE, 88, 286-290 (1991).

 W. N. Howald and D. J. Porubek, "Quantification of 3-(2-hydroxypropyl)-5-methyl-2-oxazolidinone (HMPO) in Groundwater and Sludge by Isotope Dilution Gas Chromatography/Mass Spectrometry," Environ. Sci. Technol., 28, 682-685 (1994).

 J. M. Neal, W. N. Howald, K. L. Kunze, R. F. Lawrence and W. F. Trager, "Application of Negative Ion Chemical Ionization Dilution Gass Chromatography/Mass Spectrometry to Single Dose Bioavailability Studies of Mefloquine," J. Chromatogr., B. 661, 263-269 (1994).

 S. B. Park, W. N. Howald and J. R. Cashman, "S-oxidative cleavage of farnesylcysteine and farnesylcysteine methyl ester by the flavin-containing monooxygenase," Chem. Res. Toxicol., 7, 191-198 (1994).

 H. B. Skubatz, E. Svee, B. S. Moore, W. N. Howald, W. Tang and B. J. D. Meeuse, "Inverse Correlation Between Oleic Acid and Its Positional Isomer, cis-Vaccine Acid, in the Appendix fo Sautomatum Guttatum During Anthesis," Plant Physiol., 107, 1433-1438 (1995).

 H. Wang, K. B. Lim, R. F. Lawrence, W. N. Howald, J. A. Taylor, L. H. Ericsson, K. A. Walsh and M. Hackett, "Stability enhancement for peptide analysis by electrospray using the triple quadrupole mass spectrometer," Anal. Biochem., 250, 162-168 (1997).

 A. Y. Bagrov, O. V. Fedorova, R. I. Dmitrieva, W. N. Howald, A. P. Hunter, E. A. Kuznetsova and V. M. Shpen, "Characterization of a urinary bufodienolide Na+, K+-ATPase inhibitor in patients after acute myocardial infarction," Hypertension, 31, 1097-1103 (1998).

 K. A. Regal, W. N. Howald, R. M. Peter, C. A. Gartner, K. L. Kunze and S. D. Nelson, "Subanomolar quantification of caffeine's in vitro metabolites by stable isotope dilution gas chromatography-mass spectrometry," J. Chromatogr. B. Biomed. Sci. Appl., 708, 75-85 (1998).

 M. A. Gibbs, K. L. Kunze, W. N. Howald and K. E. Thummel, "Effect of inhibitor depletion on inhibitory potency: tight binding inhibition of CYP3A by clotrimazole," Drug Metab. Dispos., 27, 596-599 (1999).

 T. F. Kalhorn, S. Ren, W. N. Howald, R. F. Lawrence and J. T. Slattery, "Analysis of cyclophosphamide and five metabolites from human plasma using liquid chromatography-mass spectrometry and gas chromatography-nitrogen-phosphorus detection," J. Chromatogr. B. Biomed. Sci. Appl., 732, 287-298 (1999).

 H. Chen, W. N. Howald and M. R. Juchau, "Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis of all-trans-retinol oxidation by human P-450 cytochromes," Drug Metab. Dispos., 285, 315-322 (2000).

 W. D. Nes, Y. O. Lukyanenko, Z. H. Jia, S. Quideau, W. N. Howald, T. K. Pratum, R. R. West and J. C. Hutson, "Identification of the lipophilic factor produced by macrophages that stimulates steroidogenesis," Endocrinology, 141, 953-958 (2000).

 S. Madani, W. N. Howald, R. F. Lawrence and D. D. Shen, "Analysis of hydroxylated and N-dealkylated metabolites of terfenadine in microsomal incubates by liquid chromatography-mass spectrometry," J. Chromatogr. B. Biomed. Sci. Appl., 741, 145-153 (2000).

 J. W. Lampe, H. E. Skor, S. Li, K. Wahala, W. N. Howald and C. Chen, "Wheat bran and soy protein feeding do not alter urinary excretion of the isoflavan equol in premenopausal women," J. Nutr., 131, 740-744 (2001).

 T. G. Shang, S. L. Doty, A. M. Wilson, W. N. Howald and M. P. Gordon, "Trichloroethylene Oxidative Metabolism in Plants: The Trichloroethanol Pathway," Phytochem., 58, 1055-1065 (2001).

 H. Skubatz and W. N. Howald, ìcis-Vaccenic Acid and Squalene in the Mitochondria of the Sauromatum guttatum Appendix,î Phyton, 42, 189-198 (2002).

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This page last updated: January 20, 2004