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Atropine: A sensitive gas chromatography—mass spectrometry assay and prepharmacokinetic studies

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Abstract

A novel assay method for the determination of atropine in biological fluids is presented. Atropine is extracted and subsequently hydrolyzed. The generated tropine is then derivatized to heptafluorobutyryl-tropine, which is measured by GLC-MS. Base peaksm/z 124 andm/z 127 are simultaneously monitored. Deuterated atropine serves as internal standard. This specific and sensitive assay permits a delineation of the disposition pharmacokinetics in humans after i.v. administration of the drug.

Prepharmacokinetic studies determined pK a values for atropine and tropine of 9.56 and 10.35 respectively at 22°C. Solvent partitioning experiments showed that atropine exerts a significantly larger lipophilicity than tropine. This was consistent with the observed higher plasma protein binding and erythrocyte buffer partitioning of atropine (12%, 1.2) compared with tropine (0%, 0.85) at 37°C and pH 7.4. Plasma protein binding and erythrocyte partitioning of both compounds were concentration independent and invariable in the presence or absence of each other.

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References

  1. L.S. Goodman andA. Gilman,The Pharmacological Basis of Therapeutics 5th edn., p. 516. The MacMillan Company, New York 1977.

    Google Scholar 

  2. M. Tønnesen,The excretion of atropine and allied alkaloids in urine, Acta Pharmac.6, 147–164 (1950).

    Google Scholar 

  3. R.E. Gosselin, J.D. Gabourel andJ.H. Wills,The fate of atropine in man, Clin. Pharmac. Ther.1, 597–603 (1960).

    Google Scholar 

  4. S.C. Kalser The fate of atropine in man, Ann. N.Y. Acad. Sci.179, 667–683 (1971).

    PubMed  Google Scholar 

  5. S.C. Kalser,andP.L. McLain,Atropine metabolism in man, Clin. Pharmac. Ther.11, 214–227 (1970).

    Google Scholar 

  6. R.J. Wurzburger, R.L. Miller, H.G. Boxenbaum andS. Spector,Radio immunoassay of atropine in plasma, Exp. Ther.203, 435–441 (1977).

    Google Scholar 

  7. W.F. Bayne, F.T. Tao andN. Crisologo,Submicrogram assay for scopolamin in plasma and urine, J. Pharm. Sci.64, 288–291 (1975).

    PubMed  Google Scholar 

  8. L.S. Goodman andA. Gilman,The Pharmacological Basis of Therapeutics, 5th edn, p. 515. The MacMillan Company, New York 1977.

    Google Scholar 

  9. G.C. Schmidt, T.E. Eling andJ.C. Drach,Synthesis of tropine labelled atropine I, micromethods for the synthesis of tropine and for its esterification with tropic acid, J. Pharm. Sci.56, 215–221 (1976).

    Google Scholar 

  10. F. Blicke, H. Raffelson andB. Barna,The preparation of tropic acid, J. Amer. Clin. Soc.74, 253 (1952).

    Article  Google Scholar 

  11. J. Van de Kamp andMeyer Sletzinger,Production of tropine, U.S. Patent Office, U.S. Pat. 2,366,760 (1945).

  12. A. Stoll, E. Jucker andA. Lindemann,Process for the preparation of alkoxy-tetrahydrofuranes, U.S. Patent Office, U.S. Pat. 2,746,976 (1956).

  13. A. Albert andE.P. Serjeant,The Determination of Ionization Constants, p. 9, Chapman and Hall, London 1971.

    Google Scholar 

  14. A. Albert andE.P. Serjeant,The Determination of Ionization Constants, p. 281. Chapman and Hall, London 1971.

    Google Scholar 

  15. P.H. Hinderling, J. Brès andE.R. Garrett,Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite, J. Pharm. Sci.,63, 1684–1690 (1974).

    PubMed  Google Scholar 

  16. P.H. Hinderling,Comparative studies of the protein binding of digoxin and its metabolites, Agents and Actions7, 379–382 (1977).

    Article  PubMed  Google Scholar 

  17. A. Roos andP.H., Hinderling,Protein binding and erythrocyte partitioning of the antirheumatic proquazone, J. Pharm. Sci. (in press).

  18. L.T. Skeggs Jr andH. Hochstrasser,Multiple automatic sequential analysis, Clin. Chem.,10, 918–936 (1964).

    PubMed  Google Scholar 

  19. C.B. Laurell,Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies, Analyt. Biochem.15, 45–50 1966.

    Article  PubMed  Google Scholar 

  20. Documenta Geigy, 7th edn (EdsK. Diem andC. Lentner), p. 582. Ciba-Geigy Corporation, Ardsley, New York 1975.

    Google Scholar 

  21. P. Zwirblis, J. Socholitsky andA. Kondritzer,The kinetics of the hydrolysis of atropine. J. Am. Pharmaceut. Ass. Sci. Ed.45, 450–454 1956.

    Google Scholar 

  22. A. Albert andE.P. Serjeant,The Determination of Ionization Constants, p. 18, Chapman and Hall, London 1971.

    Google Scholar 

  23. L.S. Schanker, P.A. Nafpliotis andJ.M. Johnson,Passage of organic bases into human red cells, J. Pharmac. Exp. Therap.113, 325–331 1961.

    Google Scholar 

  24. U. Abshagen, H. Kewitz andN. Rietbrock,Distribution of digoxin, digitoxin and ouabain between plasma and erythrocytes in various species,. Naunyn-Schmiedebergs Arch. Pharmak.270, 105–116 (1971).

    Article  Google Scholar 

  25. W. Dieterle, J. Wagner andJ.W. Faigle,Binding of chlorthalidone (Hygroton ®)to blood components in man, Eur. J. Clin. Pharmac.10, 37–42 (1976).

    Article  Google Scholar 

  26. B.D. Davis,The binding of sulfonamide drugs by plasma proteins. A factor in determining the distribution of drugs in the body, J. Clin. Invest.22, 753–762 (1943).

    Google Scholar 

  27. M. Gibaldi andD. Perrier,Pharmacokinetics,. p. 45. Marcel Decker, New York 1975.

    Google Scholar 

  28. D.S. Riggs,The Mathematical Approach to Physiological Problems, p. 146. Williams and Wilkins, Baltimore 1963.

    Google Scholar 

  29. J.M. Kolthoff,Die Dissoziationskonstante, das Löslichkeitsprodukt und die Titrierbarkeit von Alkaloiden, Biochem. Z.162, 289–353 (1925).

    Google Scholar 

  30. F. Müller,Die Potentiometrische Bestimmung von Alkaloiden an der Wasserstoffelektrode, Z. für Elektrochemie30, 587–600 (1924).

    Google Scholar 

  31. The Merck Index, 9th edn. Merck and Co. Rahway 1968

  32. A. Alberti,Ionization, pH and biological activity, Pharmac. Review4, 136–167 (1952).

    Google Scholar 

  33. E. Krüger-Thiermer,Dosage schedule and pharmacokinetics in chemotherapy, J. Am. Pharmaceut. Ass. Sci. Ed.49, 311–313 (1960).

    Google Scholar 

  34. P. Spring,Die Bindung einiger Sulfanilamide an die Bluteiweisskörper des Menschen, Drug Res.16, 346–354 (1966).

    Google Scholar 

  35. P. Kramer, E. Köthe.,J. Saul andF. Scheler,Uraemic and normal plasma protein binding of various cardiac/glycosides under ‘in vivo’ conditions, Eur. J. Clin. Invest.4, 53–58 (1974).

    PubMed  Google Scholar 

  36. M. Tønnesen,On the absorption of atropine to plasma proteins, Acta pharmacol. et toxicol.12, 247–250 (1956).

    Google Scholar 

  37. J. Judis,Binding of amphetamine, atropine, epinephrine and histamine to human serum proteins, Can. J. Pharm. Sci.14, 46–50 (1979).

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Biocenter, University of Basel, 4056, Basel, Switzerland

    M. Eckert & P. H. Hinderling

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  1. M. Eckert
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  2. P. H. Hinderling
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Eckert, M., Hinderling, P.H. Atropine: A sensitive gas chromatography—mass spectrometry assay and prepharmacokinetic studies. Agents and Actions 11, 520–531 (1981). https://doi.org/10.1007/BF02004716

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