Abstract
The simultaneous determination of preparations used for multicomponent intravenous anesthesia (Promedol, tramadol, ketamine, diazepam, Thiopental, and phentanyl) and of their metabolites in blood and urine of surgical patients by chromatography-mass spectrometry was considered. Artifacts due to the Chromatographie interference of various preparations and their metabolites were revealed. The lability of the anesthetics and their metabolites in the course of sample preparation and analysis by gas chromatography (GC) was examined. The degradation products of the test preparations responsible for the generation of false positive results were found. Phentanyl, Promedol, ketamine, tramadol, Thiopental, diazepam, and their metabolites excreted with urine in the free forms were determined in the whole blood and urine of surgical patients. Bound forms of metabolites and the initial medicinal preparations excreted as complexes with glucuronic acid and other acids were also determined in urine. Metabolites and impurity substances in the intravenous anesthetics with similar mass spectra and retention times were distinguished. Methodological recommendations concerning the analysis of difficult-to-separate (by capillary gas chromatography) pairs of substances used for intravenous anesthesia and their metabolites are given. The following pairs of components are difficult to separate: Norpromedol-2-methylamino-5-chlorobenzophenon (a product of diazepam hydrolysis), norketamine-Promedol, and anhydrotramadol (a GC artifact)-ketamine. The cumulation of an impurity substance from the tramadol preparation, identified by us as epoxytramadol, in the body was examined.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Mashkovskii, M.A.,Lekarstvennye sredstva (Medicinal Preparations), Vilnius: Gamta, 1994, vol. 1, p. 152.
Kuzin, M.I., Efimova, N.V., and Osipova, N.A.,Neiroleptoanal’geziya v khirurgii (Neuroleptic Analgesia in Surgery), Moscow: Meditsyna, 1976, p. 311.
Bunyatyan, A.A., Ryabov, G.A., and Manevich, A.Z.,Anesteziologiya i reanimatologiya (Anesthesiology and Reanimation), Moscow: Meditsyna, 1984, p. 509.
Eremin, S.K., Izotov, B.N., and Veselovskaya, N.V.,Analiz narkoticheskikh sredstv (Analysis of Narcotic Substances), Moscow: Mysl’, 1993, p. 259.
Rudenko, B.A., Savchuk, S.A., and Brodskii, E.S.,Zh. Anal. Khim., 1996, no. 2, p. 182.
Adams, J.D., Baillie, T.A., Tervor, A.J., and Castagnoli, N.,Biomed. Mass Spectrom., 1981, vol. 8, no. 11, p. 527.
Savchuk, S.A., Rudenko, V.A., Davydova, N.A., and Brodskii, E.S.,Zh. Anal. Khim., 1995, no. 11, p. 1324.
Savchuk, S.A., Brodskii, E.S., Rudenko, B.A., Formanovskii, A.A., and Davydova, N.A.,Zh. Anal. Khim., 1997, vol. 52, no. 12, p. 1299.
Savchuk, S.A., Brodskii, E.S., Formanovskii, A.A., Erofeev, V.V., Babanova, E.V., Chistyakov, V.V., Rabinovich, M.L., Dolina, O.A., and Rudenko, B.A.,Zh. Anal. Khim., 1998, vol. 53, no. 6, p. 663.
Raffa, R.B., Friderichs, E., Reimann, W., Shank, R.P., and Codd, E.E.,J. Pharmacol. Exp. Then, 1993, vol. 267, no. 1, p. 331.
Collart, L., Luthy, C, Favarioconstantin, C, and Dayer, P,Schweiz. Med. Wochenschr., 1993, vol. 123, no. 47, p. 2241.
Veselovskaya, N.V., Kislun, Yu.V, Eremin, S.K., Izotov, B.N., Vyatchanina, A.P., Dorogokupets, O.B., Morozova, E.B., and Kovalenko, A.E.,Sud.-Med. Ekspert., 1996, vol. 4, p. 38.
Savchuk, S.A., Brodsky, E.S., Rudenko, B.A., Formanovsky, A.A., Erofeev, V.V., and Chistyakov, V.V., Abstracts of Papers,Int. Congr. on Anal. Chem., Moscow., Russia, 1997, Moscow, 1997, vol. 1, p. E-75.
Veselovskaya, N.V., Izotov, B.N., and Savchuk, S.A.,Vopr. Narkol., 1998, no. 2, p. 43.
Klyuev, N.A., Bokovikova, T.N., Gorozhankin, S.K., Gernikova, E.P., and Nesterova, G.A.,Khim.-Farm. Zh., 1992, nos. 11–12, p. 103.
Meier, P. and Thormann, W.,J. Chromatogr., 1991, vol. 559, nos. 1-2, p. 505.
Hosotsubo, H.,Chromatographia, 1988, vol. 25, no. 10, p. 887.
Ebling, W.F., Harapat, S.R., Millswilliams, L., and Stanski, D.R.,J. Chromatogr., Biomed. Appl., 1989, vol. 490, no. 2, p. 339.
Celardo, A. and Bonati, M.,J. Chromatogr., Biomed. Appl., 1990, vol. 527, no. 1, p. 220.
Moore, J.M., Allen, A.C., Carr, S.M., and Cooper, D.A.,Anal. Chem., 1986, vol. 58, no. 8, p. 1656.
Borovikova, T.N., Klyuev, N.A., Gorozhankin, S.K., Stronova, L.A., and Suranova, A.V.,Khim.-Farm. Zh., 1993, no. 7, p. 58.
Wilson, T.D., Maloney, T., and Amsden, W.B.,J. Chromatogr., 1988, vol. 445, no. 1, p. 299.
Woestenborghs, R.J.H., Heykants, J.J.P., Scott, J.C., and Stanski, D.R.,Anesthesiology, 1987, vol. 67, no. 1, p. 85.
Kintz, P., Chaumont, A.J., Mangin, P., and Lugnion, A.A.,J. Chromatogr., Biomed. Appl., 1989, vol. 489, no. 2, p. 459.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Savchuk, S.A., Brodskii, E.S., Formanovskii, A.A. et al. Artifacts in the determination of intravenous anesthetics by gas chromatography-mass spectrometry: Tramadol, the correlation between the structures of metabolites and impurity substances. J Anal Chem 55, 384–396 (2000). https://doi.org/10.1007/BF02757777
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02757777