Advertisement

Pharmaceutisch weekblad

, Volume 1, Issue 1, pp 417–424 | Cite as

Determination of tricyclic antidepressants and some of their metabolites in serum by straight phase HPLC

  • D. R. A. Uges
  • P. Bouma
Original Articles

Abstract

The correlation between blood levels of tricyclic antidepressants and clinical effect is still conflicting. Nevertheless in toxicology, clinical pharmacy and pharmacology a rapid, selective and sensitive assay for these drugs and their metabolites is needed.

AHplc-method is presented for the rapid determination of amitriptyline, nortriptyline, clomipramine, desmethylclomipramine, imipramine, desipramine, doxepin, desmethyldoxepin, protriptyline, trimipramine and maprotiline. The determination is completed within 10 minutes after one single extraction (14 minutes with 10-hydroxynorthriptyline). Using this method a mean coefficient of variation of 3.3% (n=10 per drug, at 100μg/l serum) was found. The determination is easy to combine with an assay for anticonvulsant drugs on the same column (47), and suitable for routine monitoring of the concentration of many major tranquillizers.

Keywords

Imipramine Amitriptyline Clomipramine Nortriptyline Prussian Blue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Seppaelae, T., R. Liljequist, M. Linnoila, K. F. Overo andF. Dorrity (1977) Correlations between serum Ami- and nortriptyline concentrations and psychomotor performance,Acta Pharmacol. Toxicol. 41, 472–480.Google Scholar
  2. 2.
    Burrows, G.D., K. P. Maguire, B. A. Scoggins, J. Stevenson andB. Davies (1977) Plasma Nortriptyline and Clinical response — A study using changing plasma levels,Psychol. Med. 7, 87–91.CrossRefPubMedGoogle Scholar
  3. 3.
    Coppen, A., K. Ghose, S. Montgomery, V. A. Rama Rad, J. Bailey, J. Christiansen, P. L. Mikkleson, H. M. Van Praag, F. Van De Poel, E. J. Minsker, V. G. Kozulja, N. Matussek, G. Kungkunz andA. Jorgensen (1978) Amitriptyline plasma-concentration and clinical effect. A world health organisation collaborative study,Lancet I, 63–66.CrossRefGoogle Scholar
  4. 4.
    Kragh-Sorensen, P., C. E. Hansen, P.C. Baastrup andE. F. Hvidberg (1976) Self-inhibiting action of Nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression,Psychopharmacologia 45 (3), 305–312.CrossRefPubMedGoogle Scholar
  5. 5.
    Ziegler, V. E., P. J. Clayton, J. R. Taylor, B. Tee andJ. T. Biggs (1976) Nortriptyline plasma Levels and Therapeutic respons,Clin. Pharmacol. Therap. 20, 458–463.CrossRefGoogle Scholar
  6. 6.
    Glassman, A. H., J. M. Perel, M. Shostak, S. J. Kantor andJ. L. Fleiss (1977) Clinical implication of imipramine plasma levels for depressive illness,Arch. Gen. Psychiatry 34, 197–204.CrossRefPubMedGoogle Scholar
  7. 7.
    Kupfer, D. J., I. Hanin, D. G. Spiker, T. Grau andP. Coble (1977) Amitriptyline plasma Levels and Clinical response in primary depression,Clin. Pharmacol. Therap. 22, 904–911.CrossRefGoogle Scholar
  8. 8.
    Ziegler, V.E., P. J. Clayton andJ. T. Biggs (1977) A comparison study of amitriptyline and nortriptyline with plasma levels,Arch. Gen. Psychiatry 34, 607–612.CrossRefPubMedGoogle Scholar
  9. 9.
    Braithwaite, R. A., andR. Goulding (1972) Plasma concentrations of amitriptyline and clinical respons,Lancet I, 1297–1300.CrossRefGoogle Scholar
  10. 10.
    Montgomery, S., R. Braithwaite, S. Dawling andR. Mcauley (1978) High plasma nortriptyline levels in the treatment of depression 1,Clin. Pharmacol. Therap. 23, 309–314.CrossRefGoogle Scholar
  11. 11.
    Bryan, C. K., J. A. Ludy, S. H. Hak, R. Roberts andW. R. Marshall (1976) Overdose with tricyclic antidepressants,Drug Intell. Clin. Pharm. 10, 380–384.Google Scholar
  12. 12.
    Stoel, I., F. Hagemeyer andC. Hilvering (1977) Blijvend totaal atrioventriculair block na amitriptylineintoxicatie,Ned. Tijdschr. Geneesk. 121, 1096–1099.Google Scholar
  13. 13.
    Biggs, J. T., S. S. Chang, W. R. Sherman andW. H. Holland (1976) Measurement of Tricyclic Antidepressant levels in an outpatient clinic,J. Nerv. Ment. Dis. 162 (1), 46–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Kragh-Sorensen, P., C. E. Hansen, P. C. Baastrup andE. F. Hvidberg (1976) Therapeutic control of plasma concentrations and long-term effect of Nortriptyline in recurrent affective disorders,Pharmakopsychiatr. Neuropsychopharmakol. 9, 178–182.CrossRefPubMedGoogle Scholar
  15. 15.
    Westenberg, H. G., R. A. De Zeeuw, H. De Cuyper, H. M. Van Praag andJ. Korf (1977) Bioanalysis and pharmacokinetics of Clomipramine and Desmethylclomipramine in man by means of liquid chromatography,Postgrad. Med. J. 53 (suppl 4), 124–130.PubMedGoogle Scholar
  16. 16.
    Ziegler, V. E., J. T. Biggs, L. T. Wylie, W. H. Coryell, K. M. Hanifl, D. J. Hawf andS. H. Rosen (1978) Protriptyline kinetics,Clin. Pharmacol. Therap. 23, 580–584.CrossRefGoogle Scholar
  17. 17.
    Ziegler, V. E., J. T. Biggs, L. T. Wylie, S. H. Rosen, D. J. Hawf andW. H. Coryell (1978) Doxepine kinetics,Clin. Pharmacol. Therap. 23, 573–579.CrossRefGoogle Scholar
  18. 18.
    Moody, J. P., S. F. Whyte, A. J. Macdonald andG. J. Naylor (1977) Pharmacokinetic aspects of protriptyline plasma levels,Eur. J. Clin. Pharmacol. 11, 51–56.CrossRefPubMedGoogle Scholar
  19. 19.
    Ziegler, V. E., andJ. T. Biggs (1977) Tricyclic plasma levels effect of age, race, sex and smoking,J. Am. Med. Assoc. 238, 2167–2169.CrossRefGoogle Scholar
  20. 20.
    Jorgensen, A. (1977) Comparative bioavailability of a sustained release preparation of Amitriptyline and conventional tablets,Eur. J. Clin. Pharmacol. 12, 187–190.CrossRefPubMedGoogle Scholar
  21. 21.
    Nagy, A., andR. Johansson (1975) Plasma levels of imipramine and desimipramine in man after different routes of administration,Naunyn Schiedebergs Arch. Pharmacol. 290, 145–160.CrossRefGoogle Scholar
  22. 22.
    Nies, A., D. S. Robinson, M. J. Friedman, R. Green, T. B. Cooper, C. L. Ravaris andJ. O. Ives (1977) Relationship between age and tricyclic antidepressant plasma levels,Am. J. Psychiatry 134, 790–793.CrossRefPubMedGoogle Scholar
  23. 23.
    Carr, A. C., andR. P. Hobson (1977) High serum concentrations of antidepressants in elderly Patients (Letter),Brit. Med. J. 2, 1151.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Avery, G. S. (1976)Drug Treatment, Principles and Practice of Clinical Pharmacology and Therapeutics, Ed. 11. Adis Press, Sydney.Google Scholar
  25. 25.
    Howarth, A. T. (1977) A simple method for the determination of therapeutic levels of Clomipramine, Imipramine and Desimipramine,Postgrad. Med. J. 53 (suppl. 4), 131–135.PubMedGoogle Scholar
  26. 26.
    Fenimore, D. C., C. M. Davis andC. J. Meyer (1978) Determination of drugs in plasma by High-Performance Thin-Layer Chromatography,Clin. Chem. 24, 1386–1392.PubMedGoogle Scholar
  27. 27.
    Wallace, J. E., andJ. D. Biggs (1969) Colorimetric determination of imipramine in biologic specimens,J. Forensic Sci. 14, 528.PubMedGoogle Scholar
  28. 28.
    Kaul, P. N., L. R. Whitfield andM. L. Clark (1978) Quantitative determination of amitriptyline in blood,J. Pharm. Sci. 67, 60–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Lucek, R., andR. Dixon (1977) Specific Radioimmunoassay for Amitriptyline and nortriptyline in plasma,Res. Commun. Chem. Pathol. Pharmacol. 18, 125–136.PubMedGoogle Scholar
  30. 30.
    Read, G. F., andD. Riad-Fahmy (1978) Determination of tricyclic antidepressant, Clomipramine (Anafranil), in plasma by a specific Radioimmunoassay procedure,Clin. Chem. 24, 36–40.PubMedGoogle Scholar
  31. 31.
    Maguire, K. P., G. D. Burrows, J. P. Coghlan andB. A. Scoggins (1976) Rapid Radioisotopic procedure for determination of Nortriptyline in plasma,Clin. Chem. 22, 761–764.PubMedGoogle Scholar
  32. 32.
    Loh, A., F. R. Zuleski andF. I. Di Carlo (1977) Radiochemical glc assay for Nortriptyline in human plasma,J. Pharm. Sci. 66, 1056–1058.CrossRefPubMedGoogle Scholar
  33. 33.
    Bailey, D. N., andP. I. Jatlow (1976) Gas-chromatographic analysis for therapeutic concentration of imipramine and desimipramine in plasma, with use of a nitrogen detector,Clin. Chem. 22, 1697–1701.PubMedGoogle Scholar
  34. 34.
    Connor, J. N., G. F. Johnson andH. M. Solomon (1977) Quantitation of Amitriptyline and Nortriptyline in human serum,J. Chromatog. 143, 415–421.CrossRefGoogle Scholar
  35. 35.
    Dorrity, F. Jr.,M. Linnoila andR. L. Habig (1977) Therapeutic monitoring of Tricyclic Antidepressants in plasma by Gas chromatography,Clin. Chem. 23, 1326–1328.PubMedGoogle Scholar
  36. 36.
    Hucker, H. B., andS. C. Stauffer (1977) Rapid, sensitive Gas-Liquid Chromatographic method for determination of Amitriptyline and Nortriptyline in plasma using a nitrogen-sensitive detector,J. Chromatog. 138, 437–442.CrossRefGoogle Scholar
  37. 37.
    Nyberg, G., andE. M'Artensson (1977) Quantitative analysis of Tricyclic Antidepressants in serum from psychiatric patients,J. Chromatog. 143, 491–497.CrossRefGoogle Scholar
  38. 38.
    Bailey, D. N., andP. I. Jatlow (1976) Gas-Chromatographic analysis for therapeutic concentrations of Amitriptyline and Nortriptyline in plasma, with use of a Nitrogen detector,Clin. Chem. 22, 777–781.PubMedGoogle Scholar
  39. 39.
    Dubois, J. P., W. Kueng, W. Theobald andB. Wirz (1976) Measurement of Clomipramine,N-desmethylclomipramine, Imipramine and Dehydroimipramine in biological fluids by selective ion monitoring, and Pharmacokinetics of Clomipramine,Clin. Chem. 22, 892–897.PubMedGoogle Scholar
  40. 40.
    Garland, W. A. (1977) Quantitative determination of Amitriptyline and its principal metabolite Nortriptyline, byGlc/Chemical Ionization Mass Spectrometry,J. Pharm. Sci. 66, 77–81.CrossRefPubMedGoogle Scholar
  41. 41.
    Wilson, J. M., L. J. Williamson andV. A. Raisys (1977) Simultaneous Measurements of secondary and tertiary Tricyclic Antidepressants byGs/ms Chemical Ionization Mass Fragmentography,Clin. Chem. 23, 1012–1017.PubMedGoogle Scholar
  42. 42.
    Jenkins, R. G., andR. O. Friedel (1978) Analysis of tricyclic antidepressants in human plasma by glc/ chemical Ionization Mass Spectrometry with selected ion monitoring,J. Pharm. Sci. 67, 17–23.CrossRefPubMedGoogle Scholar
  43. 43.
    Watson, I. D., andM. J. Stewart (1977) Quantitative determination of Amitriptyline and Nortriptyline in plasma by High-Performance Liquid Chromatography,J. Chromatog. 132, 155–159.CrossRefGoogle Scholar
  44. 44.
    Westenberg, H. G., B. F. Drenth, R. A. De Zeeuw, H. De Cuyper andJ. Korf (1977) Determination of Clomipramine and Desmethylclomipramine in plasma by means of Liquid Chromatography,J. Chromatog. 142, 725–733.CrossRefGoogle Scholar
  45. 45.
    Kraak, J. C., andP. Bijster (1977) Determination of Amitriptyline and some of its metabolites in blood by High-Pressure Liquid Chromatography,J. Chromatog. 143, 499–512.CrossRefGoogle Scholar
  46. 46.
    Vandemark, F. L., R. F. Adams andG. J. Schmidt (1978) Liquid Chromatographic procedure for Tricyclic drugs and their metabolites in plasma,Clin. Chem. 24, 87–91.PubMedGoogle Scholar
  47. 47.
    Uges, D. R. A., andP. Bouma (1978) Hogedruk-vloeistofchromatografische bepaling van fenobarbital, fenytoine, ethosuximide, carbamazepine and carbamazepine-epoxide in serum,Med. Ned. Ver. Ziekenhuisapothekers 35, 320–323 (copies of an English translation are obtainable from the authors).Google Scholar
  48. 48.
    Uges, D. R. A., andP. Bouma (1976) Een eenvoudige bepaling van Clonazepam in serum met behulp van hogedruk-vloeistof-chromatografie,Pharm. Weekblad 111, 877–882.Google Scholar
  49. 49.
    Uges, D. R. A., andP. Bouma (1978) An improved determination of clonazepam in serum ByHplc,Pharm. Weekblad 113, 1156–1158.Google Scholar
  50. 50.
    Uges, D. R. A., andP. Bouma (1978) Bereiding van kolommen voor een hoge druk vloeistofchromatograaf.Med. Ned. Ver. Ziekenhuisapothekers 35, 316–319 (copies are obtainable from the authors).Google Scholar
  51. 51.
    Moyes, R. B., andI. C. A. Moyes (1977) Measurement of plasma antidepressant levels by high-performance liquid chromatography,Postgraduate Med. J. 53 (suppl.4), 117–123.Google Scholar

Copyright information

© Bohn, Scheltema & Holkema 1979

Authors and Affiliations

  • D. R. A. Uges
    • 1
  • P. Bouma
    • 1
  1. 1.Laboratory for Toxicology and Clinical Pharmacy, Department of PharmacyState University HospitalGroningenThe Netherlands

Personalised recommendations