Skip to main content

Gas Chromatography-Mass Spectrometry

  • Chapter
Concepts in Biochemical Pharmacology

Abstract

In choosing a method by which to identify drug metabolites, the quantity of material which is available is a prime consideration. In this regard, pharmacologists find themselves midway between natural products chemists and biochemists. Usually the former has reasonably large quantities of material available in a relatively high state of purity. The biochemist on the other hand, is usually forced to deal with submicrogram quantities; radioactivity may be the only objective evidence of the existence of a compound. This is a consequence of the biochemist’s use of purified enzyme preparations which only allow for the conversion of mg quantities under the carefully controlled conditions he usually wishes to maintain. Attempts to scale up such processes may bring about a whole new set of problems. The pharmacologist interested in drug metabolism deals with enzyme systems as present in intact organs or at least parts of organs (liver slices, etc.), and in general this permits conversion of somewhat larger quantities. In fact, most drugs in use today are employed at mg rather than μg levels and so the investigation of their metabolism is at least practicable. This chapter discusses the advantages and disadvantages of mass spectrometry, especially as combined with gas chromatography, for such investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adlercreutz, H., Johansson, C.J., Luukkainen, T.: Gas chromatographic and mass spectrometric studies in the influence of metabolites of bis (p-acetoxyphenyl) cyclohexylidenemethane on the estimation of estrogens in urine. Ann. Med. exp. Fenn. 45, 269–276 (1967).

    PubMed  CAS  Google Scholar 

  • Änggärd, E., Sedvall, G.: Gas chromatography of catecholamine metabolites using electron capture detection and mass spectrometry. Anal. Chem. 41, 1250–1256 (1969).

    Article  PubMed  Google Scholar 

  • Alber, L.L.: All-purpose gas-liquid chromatographic column for pharmaceuticals. J. Ass. Off. Anal. Chem. 52, 1295–1300 (1969).

    CAS  Google Scholar 

  • Anders, M.W., Mannering, G.J.: Applications of gas chromatography to toxicology. Progr. chem. Tox. 3, 121–218 (1967).

    CAS  Google Scholar 

  • Application of Metabolic Data to the Evaluation of Drugs: A report prepared by the Committee on Problems of Drug Safety of the Drug Research Board, National Academy of Sciences — National Research Council: Clin. Pharmacol. Ther. 10, 607–634 (1969).

    Google Scholar 

  • Arnold, W., Grutzmacher, W.F.: Massenspektrometrischer Nachweis von Arzneimittelmetaboliten (Barbiturate, Noludar, Pyramidon) in Rahmen der forensischen Analyse. Fresenius’ Z. anal. Chem. 247, 179–188 (1969).

    Article  CAS  Google Scholar 

  • Audier, H., Fetizon, M., Ginsburg, D., Mandelbaum, A., Rull, T.: Mass spectrometry of morphine alkaloids. Tetrahedron Letters 1, 13–22 (1965).

    Article  Google Scholar 

  • Bagley, G.E., Reichel, W.L., Cromartie, E.: Identification of polychlorinated biphenyls in two bald eagles by combined gas-liquid chromatography-mass spectrometry. J. Ass. Off. Anal. Chem. 53, 251–261 (1970).

    CAS  Google Scholar 

  • Ballantine, J.A., Fenwick, R.G.: The mass spectra of griseofulvin analogues. Characteristic fragmentation processes in the mass spectra of spirocyclohexenones and spirocyclohexanones containing the griseofulvin skeleton. Org. Mass. Spect. 2, 1145–1169 (1969).

    Article  CAS  Google Scholar 

  • Beckett, A.H., Tucker, G.T., Moffat, A.C.: Routine detection and identification in urine of stimulants and other drugs, some of which may be used to modify performance in sport. J. Pharm. Pharmacol. 19, 273–294 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Belasco, I.J., Reiser, R.W.: Metabolic fate of siduron in the animal. J. Agr. Food Chem. 17, 1000–1003 (1969).

    Article  CAS  Google Scholar 

  • Bellman, S.W.: Mass spectral identification of some hallucinogenic drugs. J. Ass. Off. Anal. Chem. 15, 164–175 (1968).

    Google Scholar 

  • Beynon, J.H.: Mass spectrometry and its applications to organic chemistry. Amsterdam: Elsevier 1960.

    Google Scholar 

  • Beynon, J.H., Hopkinson, J.A., Williams, A.E.: The mass spectra of some guanidines. Org. Mass. Spect. 1, 169–187 (1968).

    Article  CAS  Google Scholar 

  • Beynon, J.H., Saunders, R.A., Williams, A.E.: The mass spectra of organic molecules. Amsterdam: Elsevier 1968.

    Google Scholar 

  • Beynon, J.H., Williams, A.E.: Mass and abundance tables for use in mass spectrometry. Amsterdam: Elsevier 1963.

    Google Scholar 

  • Biemann, K.: Mass spectrometry, applications to organic chemistry. New York: McGraw-Hill 1962.

    Google Scholar 

  • Biemann, K., McCloskey, J.A.: Application of mass spectrometry to structural problems. VI. Nucleosides. J. Amer. chem. Soc. 84, 2005–2007 (1962).

    Article  CAS  Google Scholar 

  • Biemann, K., Watson, J.T.: Recording and interpretation of high resolution mass spectra of natural products as eluted from a gas chromatograph. Monatsh. Chem. 96, 305–315 (1965).

    Article  CAS  Google Scholar 

  • Biros, F.J., Walker, A.C.: Pesticide residue analysis in human tissue by combined gas chromatography-mass spectrometry. J. Agr. Food Chem. 18, 425–429 (1970).

    Article  CAS  Google Scholar 

  • Bogentoft, C., Danielsson, B.: Studies on the medicinal chemistry of oxoquinazolines. VI. Mass spectra of isomeric N-and O-alkylated 4-oxoquinazolines. Acta pharm. Suecia 6, 589–598 (1969).

    CAS  Google Scholar 

  • Broadhurst, N.A., Montgomery, M.L., Freed, V.H.: Metabolism of 2-methoxy-3,6-dichlorobenzoic acid (dicamba) by wheat and bluegrass plants. J. Agr. Food Chem. 14, 585–588 (1966).

    Article  CAS  Google Scholar 

  • Brochmann-Hanssen, E., Oke, T.O.: Gas chromatography of barbiturates, phenolic alkaloids, and xanthine bases: Flash-heater methylation by means of trimethylanflinium hydroxide. J. pharm. Sci. 58, 370–371 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Brunnee, C., Ten Noever de Brauw, M.C.: Z. Anal. Chem. 229, No. 5, 321 (1967).

    Article  Google Scholar 

  • Budzikiewicz, H., Djerassi, C.: Mass spectrometry in structural and stereochemical problems. I. Steroid Ketones. J. Amer. chem. Soc. 84, 1430–1439 (1962).

    Article  CAS  Google Scholar 

  • Budzikiewicz, H., Djerassi, C., Williams, D.H.: Interpretation of mass spectra of organic compounds. San Francisco: Holden-Day 1964.

    Google Scholar 

  • Budzikiewicz, H., Djerassi, C., Williams, D.H.: Structure elucidation of natural products by mass spectrometry. Vol. I: Alkaloids; Vol. II: Steroids, terpinoids, sugars, and miscellaneous compounds. San Francisco: Holden-Day 1964.

    Google Scholar 

  • Budzikiewicz, H., Djerassi, C., Williams, D.H.: Mass spectrometry of organic compounds. San Francisco: Holden-Day 1967.

    Google Scholar 

  • Burtis, C.A., Butts, W.C., Rainey, W.T.: Separation of the metabolites of phenacetin in urine by high-resolution anion exchange chromatography. Amer. J. clin. Path. 53, 769–777 (1970).

    CAS  Google Scholar 

  • Burtis, C.A., Warren, K.S.: Identification of urinary constituents isolated by anion-exchange chromatography. Clin. Chem. 14, 290–301 (1968).

    PubMed  CAS  Google Scholar 

  • Butenandt, A. von, Eckman, R.B., Stamm, D., Hucker, E.: Über den Sexual-Lockstoff des Seidenspinners Bombyx mori. Reindarstellung und Konstitution. Z. Naturforsch. 14b, 283–284 (1959).

    Google Scholar 

  • Chalmers, R.A., Parker, R., Simmons, H.A., Snedden, W., Watts, R.W.E.: The conversion of 4-Hydroxypyrazolo [3,4-d] pyrimidine (Allopurinol) into 4,6-dihydroxypyrazolo [3,4-d] pyrimidine (oxipurinol) in vivo in the absence of xanthine-oxygen oxidoreductase. Biochem. J. 112, 527–532 (1969).

    PubMed  CAS  Google Scholar 

  • Cheek, F.E., Newell, S., Joffe, M.: Deceptions in the illicit drug market. Science 167, 1276 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Coutts, R.T., Hindmarsh, K.W.: Mass spectra of some quinoline hydroxamine acids and related compounds. Org. Mass. Spect. 2, 681–696 (1969).

    Article  CAS  Google Scholar 

  • Coutts, R.T., Locock, R.A.: Identification of medicinal barbiturates by means of mass spectrometry. J. pharm. Sci. 57, 2096–2100 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Coutts, R.T., Locock, R.A.: The (M-43)+ ion in the mass spectra of some medicinal barbiturates. J. pharm. Sci. 58, 775–776 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Coutts, R.T., Mukherjee, G.: Identification of the aromatic hydroxyamine group by mass spectrometry. Org. Mass. Spect. 3, 63–65 (1970).

    Article  CAS  Google Scholar 

  • Creveling, C.R., Daly, J.W.: Identification of 3,4-dimethoxyphenethylamine from schizophrenic urine by mass spectroscopy. Nature (Lond.) 216, 190–191 (1967).

    Article  CAS  Google Scholar 

  • Dalgliesh, C.E., Horning, E.C., Horning, M.G., Knox, K.L., Arger, K.Y.: A gas-liquid-chromatographic procedure for separating a wide range of metabolites occuring in urine or tissue extracts. Biochem. J. 101, 792–810 (1966).

    PubMed  CAS  Google Scholar 

  • Damico, J.N., Barron, R.P.: The mass spectra of some chlorinated pesticidal compounds. Org. Mass. Spect. 1, 331–342 (1968).

    Article  CAS  Google Scholar 

  • Damico, J.N., Chen, J.Y., Costello, C.E., Haenni, E.D.: Structure of Klein’s metabolites of aldrin and of dieldrin. J. Ass. Off. Anal. Chem. 51, 48–55 (1968).

    CAS  Google Scholar 

  • Dejongh, D.C.: Mass spectrometry, Annual Review in Analytical Chemistry. Anal. Chem. 42, No. 5 169R–205R (1970).

    Article  CAS  Google Scholar 

  • Dejongh, D.C., Perricone, S.C., Gay, M.L., Korytnyk, W.: Mass spectrometry of vitamin B6: Different forms of the vitamin, its metabolites, and antimetabolites, and analogs. Org. Mass. Spect. 1, 151–166 (1968).

    Article  CAS  Google Scholar 

  • Dreyfuss, J., Cohen, A.L., Hess, S.M.: Metabolism of thiazesim, 5-(2-dimethylaminoethyl)-2,3-dehydro-2-phenyl-1,5-benzothiazepin-4 (SH)-one in the rat in vivo and in vitro. J. pharm. Sci. 57, 1505–1511 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Duckworth, H.E.: Mass spectrometry. London: Cambridge Univ. Press 1953.

    Google Scholar 

  • Duffield, A.M., Craig, J.C., Kray, L.R.: Electron impact promoted fragmentation of some phenothiazine derivatives. Tetrahedron 24, 4267–4276 (1968).

    Article  CAS  Google Scholar 

  • Emery, E.M.: Mass spectra of aromatic esters. Anal. Chem. 32, 1495–1506 (1960).

    Article  CAS  Google Scholar 

  • Eneroth, P., Hellstrom, K., Ryhage, R.: Identification of two neutral metabolites of stigma sterol found in human feces. Steroids 6, 707–719 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Ettre, L.S., Zlatkis, A.: The practice of gas chromatography. New York: Interscience 1967.

    Google Scholar 

  • Fales, H.M., Haahti, E.O.A., Luukkainen, T., Vanden Heuvel, W.J.A., Horning, E.C.: Milligram-scale preparative gas chromatography of steroids and alkaloids. Anal. Biochem. 4, 296–305 (1962).

    Article  CAS  Google Scholar 

  • Fales, H.M., Lloyd, H.A., Milne, G.W.A.: Chemical ionization mass spectrometry of complex molecules. II. Alkaloids. J. Amer. chem. Soc. 92, 1590–1597 (1970).

    Article  CAS  Google Scholar 

  • Fales, H.M., Milne, G.W.A., Vestal, M.C.: Chemical ionization mass spectrometry. J. Amer. chem. Soc. 91, 3682–3685 (1969).

    Article  CAS  Google Scholar 

  • Field, F.H.: Chemical ionization mass spectrometry. Accounts Chem. Res. 1, 42–49 (1968).

    Article  CAS  Google Scholar 

  • Field, F.H., Franklin, J.L.: Electron impact phenomena. New York: Academic Press 1957.

    Google Scholar 

  • Friedland, S.S., Lane, G.H., Longman, R.T., Train, K.E., O’Neal, M.J.: Mass spectra of steroids. Anal. Chem. 31, 169–174 (1959).

    Article  CAS  Google Scholar 

  • Friedman, A.R., Lemin, A.J.: Metabolism of 2-chloro-4,5-dimethyl phenyl N-methylcarbamate in bean plants. J. Agr. Food Chem. 15, 642–647 (1967).

    Article  CAS  Google Scholar 

  • Fukami, J.I., Yamamoto, I., Casida, J.E.: Metabolism of rotenone in vitro by tissue homogenates from mammals and insects. Science 155, 713–716 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Gardiner, J.A., Reiser, R.W., Sherman, H.: Identification of the metabolites of bromacil in rat urine. J. Agr. Food Chem. 17, 967–973 (1969).

    Article  CAS  Google Scholar 

  • Gilbert, J.N.T., Millard, B.J.: Pharmacologically interesting compounds — I: High resolution mass spectra of phenothiazines. Org. Mass. Spect. 2, 17–31 (1969).

    Article  CAS  Google Scholar 

  • Goldman, P., Milne, G.W.A., Keister, D.B.: Carbon-halogen bond clevage III. Studies on bacterial halidohydrolases. J. biol. Chem. 243, 428–434 (1968).

    PubMed  CAS  Google Scholar 

  • Granstrom, E., Samuelsson, B.: The structure of the main urinary metabolite of prostaglandin F2 α in the guinea pig. Europ. J. Biochem. 10, 411–418 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Gray, G.M.: Gas chromatography. In: Tools of biological research. Ed by H.J.B. Atkins. Vol. 3, pp. 79–97 Springfield, Ill.: Thomas 1961.

    Google Scholar 

  • Grützmacher, H.F., Arnold, W.: Massenspektren von Barbitursäurederivaten. Tetrahedron Letters 13, 1365–1374 (1966).

    Article  PubMed  Google Scholar 

  • Guarino, A.M., Conway, W.D., Fales, H.M.: Mass spectral identification of probenecid metabolites in rat bile. Europ. J. Pharmacol. 8, 244–252 (1969).

    Article  CAS  Google Scholar 

  • Gudzinowicz, B.J.: Gas chromatographic analysis of drugs and pesticides. New York: Marcel Dekker, Inc. 1967.

    Google Scholar 

  • Hammar, C.G., Hanin, I., Holmstedt, B., Kitz, R.J., Jenden, D.J., Karlen, B.: Identification of acetylcholine in fresh rat brain by combined gas chromatography-mass spectrometry. Nature (Lond.) 220, 915–917 (1968).

    Article  CAS  Google Scholar 

  • Hammar, C.G., Holmstedt, B., Ryhage, R.: Mass Fragmentography. Identification of chlorpromazine and its metabolites in human blood by a new method. Anal. Biochem. 25, 532–548 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Hoffman, D.R.: The mass spectra of tetracyclines. J. Org. Chem. 31, 792–796 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Holtzman, J., Gillette, J.R., Milne, G.W.A.: The metabolic products of naphthalene in mammalian systems. J. Amer. chem. Soc. 89, 6341–6344 (1967).

    Article  CAS  Google Scholar 

  • Holzapfel, C.W.: The isolation and structure of cyclopiazonic acid, a toxic metabolite of Penicillium Cyclopium Westling. Tetrahedron 24, 2101–2119 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Horning, M.G., Waterbury, L.D., Horning, E.C., Hill, R.M.: Placenta; transfer of drugs: Drugs and drug metabolites in the neonate. In: The foetoplacental unit. Ed. by A. Pecile and C. Finzi, pp. 305–312. Excerpta med. (Amst.) 1969.

    Google Scholar 

  • Jaakomaki, P.I., Knox, K.L., Horning, E.C., Horning, M.G.: The characterization by gas-liquid chromatography of ethyl β-D-glucosiduronic acid as a metabolite of ethanol in rat and man. Europ. J. Pharmacol. 1, 63–70 (1967).

    Article  Google Scholar 

  • Jansson, B.O., Larsson, B.T.: Analysis of organic compounds in human breath by gas chromatography-mass spectrometry. J. Lab. clin. Med. 74, 961–966 (1969).

    PubMed  CAS  Google Scholar 

  • Johnson, R.A., Herr, M.E., Murray, H.C., Reineke, L.M., Fonken, G.S.: The microbiological oxygenation of some azabicycloalkanes. J. Org. Chem. 33, 3195 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Jorg, J., Houriet, R., Spiteller, G.: Massenspektren von Pflanzenschutzmitteln. Monatsh. Chem. 97, 1064–1087 (1966).

    Article  Google Scholar 

  • Kabasakalian, P., Taggart, M., Townley, E.: Urinary excretion of chloropheniramine and its N-demethylated metabolites in man. J. pharm. Sci. 57, 856–858 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Karlen, B., Bogentoft, C.: A mass spectrometric investigation of tremorine and related acetylenic amines and amides. Acta. pharm. Suecica 6, 543–560 (1969).

    CAS  Google Scholar 

  • Kuehl, F.A., Ormond, R.E., Vandenheuvel, W.J.A.: Occurrence of 3,4-dimethoxyphenyl acetic acid in urines of normal and schizophrenic individuals. Nature (Lond.) 211, 606–608 (1966).

    Article  CAS  Google Scholar 

  • Kuntzman, R., Sernatinger, E., Tsai, I., Klutch, A.: New methodology for studies of drug metabolism. In: Importance of fundamental principles in drug evaluation Ed. by D.H. Tedeschi and R.E. Tedeschi, pp. 87–103. New York: Raven Press 1968.

    Google Scholar 

  • Lindgren, J.E., Hammer, C.G., Hessling, R., Holmstedt, B.: The chemical identity of “Hog” — a “new” hallucinogen. Amer. J. Pharm. 141, 86–90 (1969).

    PubMed  CAS  Google Scholar 

  • Llewelyn, P.M., Littlejohn, D.P.: Presented at the Pittsburgh Conference on analytical chemistry and applied spectroscopy, Pittsburgh, Pa. (1966); see also D.R. Black, R.A. Flath and R. Teranishi: Membrane molecular separators for gas chromatographic-mass spectrometric interfaces. J. Chromatographic Sci. 7, 284–289 (1969).

    Google Scholar 

  • Luukkainen, T., Adlercreutz, H.: Mass spectrometric studies in the specificity of estriol determination in urine by gas-liquid chromatography. Ann. Med. exp. Fenn. 45, 264–268 (1967).

    PubMed  CAS  Google Scholar 

  • McLafferty, F.: Mass spectrometry of organic ions. New York: Academic Press 1963.

    Google Scholar 

  • McLafferty, F.: Interpretation of mass spectra; an introduction. New York: W.A. Benjamin 1966.

    Google Scholar 

  • McNair, H.M., Bonelli, E.J.: Basic gas chromatography. Consolidated Printers for Varian Aerograph, Walnut Creek, Calf. (1967).

    Google Scholar 

  • Milne, G.W.A., Goldman, P., Holtzman, J.L.: The metabolism of 2-fluorobenzoic acid. II. Studies with 18O2. J. biol. Chem. 243, 5374–5376 (1968).

    PubMed  CAS  Google Scholar 

  • Mize, C.E., Avigan, J., Steinberg, D., Pittman, R.C., Fales, H.M., Melne, G.W.A.: A major pathway for the mammalian oxidative degradation of phytanic acid. Biochim. biophys. Acta (Amst.) 176, 720–739 (1969).

    CAS  Google Scholar 

  • Nilsson, I.M., Agurell, S., Nilsson, J.L.G., Ohlsson, A., Sandberg, F., Wahlqvist, M.: Δ1-Tetrahydrocannabinol: Structure of a major metabolite. Science 168, 1228–1229 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Palmer, K.H., Fowler, M.S., Wall, M.E., Rhodes, L.S., Waddell, W.J., Baggett, B.: The metabolism of R (+)-and RS-phenobarbital. J. Pharmacol. exp. Ther. 170, 355–363 (1969).

    PubMed  CAS  Google Scholar 

  • Palmer, K.H., Martin, B., Baggett, B., Wall, M.E.: The metabolic fate of orally administered quinidine gluconate in humans. Biochem. Pharmacol. 18, 1845–1860 (1969).

    Article  CAS  Google Scholar 

  • Plimmer, J.R., Kearney, P.O., Von Endt, D.W.: Mechanism of conversion of DDT to DDD by Aerobacter aerogenes. J. Agr. Food Chem. 16, 594–597 (1968).

    Article  CAS  Google Scholar 

  • Reed, W.T., Forgash, A.J.: Lindane: Metabolism to a new isomer of pentachlorocyclohexene. Science 160, 1232 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Reisch, J., Pagnucco, R., Alfes, H., Jantos, N., Mollmann, H.: Mass spectra of derivatives of phenylalkylamines. J. Pharm. Pharmacol. 20, 81–86 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Rhodes, R.C., Reiser, R.W., Gardiner, J.A., Sherman, H.: Identification of the metabolites of terbacil in dog urine. J. Agr. Food Chem. 17, 974–979 (1969).

    Article  CAS  Google Scholar 

  • Ryhage, R.: Use of a mass spectrometer as a detector and analyses for effluents emerging from high temperature gas liquid chromatography columns. Anal. Chem. 36, 759–764 (1964).

    Article  CAS  Google Scholar 

  • Schwartz, M.A., Bommer, P., Vane, F.M.: Diazepam metabolites in the rat: Characterization by high resolution mass spectrometry and nuclear magnetic resonance. Arch. Biochem. 121, 508–516 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, M.A., Vane, F.M., Postma, E.: Chlordiazepoxide metabolites in the rat. Characterization by high resolution mass spectrometry. Biochem. Pharmacol. 17, 965–974 (1968a).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, M.A., Vane, F.M., Postma, E.: Urinary metabolites of 7-chloro-1-(2-diethylaminoethyl)-5-(2-flurophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one dihydrochloride. J. med. Chem. 11, 770–774 (1968b).

    Article  PubMed  CAS  Google Scholar 

  • Scott, W.M., Wacks, M.E., Eskelson, C.D., Towne, J.C., Cazee, C.: The elimination of small neutral molecules and fragments in mass spectra. — I. Substituted salicyclic acids and their derivatives. Org. Mass. Spect. 1, 847–855 (1968).

    Article  CAS  Google Scholar 

  • Seibl, J.: Information on metastable transitions in the mass spectra of organic compounds. Helv. chim. Acta 50, 263–268 (1967).

    Article  CAS  Google Scholar 

  • Silverstein, R.M., Bassler, G.C.: Spectrometric identification of organic compounds. 2nd Ed. New York: Wiley, 1967.

    Google Scholar 

  • Sinshelmer, J.E., Smith, R.U.: 4,4′-Dihydroxybibenzyl, a reduction metabolite of trans-stilbene. J. pharm. Sci. 57, 713–714 (1968).

    Article  Google Scholar 

  • Sisenwine, S.F., Walkenstein, S.S.: The metabolic fate of the pteridine diuretic, Wy-5256. J. pharm. Sci. 58, 867–871 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Smith, D.L., Grostic, M.F.: Mass spectrometric identification of the metabolites of methyl N-(o-aminophenyl)-N-(3-dimethylaminopropyl) anthranilate. J. med. Chem. 10, 375–379 (1967).

    Article  PubMed  CAS  Google Scholar 

  • von Spulak, F., Claussen, V., Fehlhaber, H.W., Korte, F.: Haschisch-XIX. Cannabidiolcarbonsäure-tetrahydrocannabitriol-ester, ein neuer Haschisch-Inhaltsstoff. Tetrahedron 24, 5379–5383 (1968).

    Article  Google Scholar 

  • Stenhagen, E.: Mass spectrometry in biochemical research. Chimia 20, 346–357 (1966).

    CAS  Google Scholar 

  • Street, H.V.: Gas liquid chromatography of submicrogram amounts of drugs. IV. Identification of barbiturates, hydantoins, amides, imides, carbamates, phenylbutazone, carboxylic acids and hydrazine derivatives by direct derivative formation within the gas chromatograph. J. Chromat. 41, 358–366 (1969).

    CAS  Google Scholar 

  • Suda, T., Deluca, H.F., Schnoes, H., Blunt, J.W.: 25-Hydroxyergocalciferol: A biologically active metabolite of Vitamin D2. Biochem. biophys. Res. Commun. 35, 182–185 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Szymanski, H.A.: Biomedical applications of gas chromatography. New York: Plenum Press 1964.

    Google Scholar 

  • Thomas, D.W., Biemann, K.: The alkaloids of Voacanga africina. Lloydia 31, 1–8 (1968).

    CAS  Google Scholar 

  • Wade, A.P., Wilkinson, G.S., Dean, F.M., Price, A.W.: The isolation characterization and structure of uroterpenol, a monoterpene from human urine. Biochem. J. 101, 727–734 (1966).

    PubMed  CAS  Google Scholar 

  • White, F.A.: Mass spectrometry in science and technology. New York: Wiley 1968.

    Google Scholar 

  • Woltz, H.H., Clark, S.J.: Gas chromatography in the analysis of steroid hormones. New York: Plenum Press 1966.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1971 Springer-Verlag Berlin · Heidelberg

About this chapter

Cite this chapter

Guarino, A.M., Fales, H.M. (1971). Gas Chromatography-Mass Spectrometry. In: Brodie, B.B., Gillette, J.R., Ackerman, H.S. (eds) Concepts in Biochemical Pharmacology. Handbook of Experimental Pharmacology / Handbuch der experimentellen Pharmakologie, vol 28 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65177-9_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-65177-9_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-65179-3

  • Online ISBN: 978-3-642-65177-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics