Advertisement

Pharmaceutisch Weekblad

, Volume 12, Issue 5, pp 196–199 | Cite as

Decomposition of pilocarpine eye drops assessed by a highly efficient high pressure liquid chromatographic method

  • Paul F. M. Kuks
  • Leo E. A. Weekers
  • Pieter B. Goldhoorn
Articles

Abstract

A rapid high-resolution high pressure liquid chromatographic method was developed for assaying pilocarpine. Pilocarpine in ophthalmic solutions decomposes fairly rapidly to give isopilocarpine, pilocarpic acid and isopilocarpic acid. The quality of an ophthalmic solution can be assessed by assaying these decomposition products. Existing high pressure liquid chromatographic methods suffer from long analysis times and poor resolution. The new method uses as the mobile phase 6 ml/l of triethylamine in water (pH 2.3, adjusted with 85% phosphoric acid) at a flow of 1.5 ml/min and as the stationary phase a C18-silica 125×4,6 mm column. 2-Amino-1phenyl-1,3-propanediol is used as an internal standard. Complete separation was obtained within 8 min. Pilocarpine eye drops were stored under different conditions and then analysed for decomposition products. During heat treatment, decomposition to isopilocarpine predominated over decomposition to pilocarpic or isopilocarpic acid. However, when stored at room temperature or in a refrigerator, formation of pilocarpic acid clearly prevailed. Thus, from assessment of decomposition products, the cause of decomposition can be established.

Keywords

Chemistry, analytical Chromatography, high pressure liquid Decomposition products Drug stability Ophthalmic solutions Pilocarpine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baeschlin K, Etter JC, Moll H. Contribution à l'étude de la stabilité de la pilocarpine en milieu aqueux. 1re Communication. Identification des produits de décomposition de la pilocarpine. Pharm Helv Acta 1969;44:301–9.Google Scholar
  2. 2.
    Baeschlin K, Etter JC. Contribution à l'étude de la stabilité de la pilocarpine en milieu aqueux. 2e Communication. Étude cinétique de l'hydrolyse de la pilocarpine. Pharm Acta Helv 1969;44:339–47.Google Scholar
  3. 3.
    Baeschlin K, Etter JC. Contribution à l'étude de la stabilité de la pilocarpine en milieu aqueux. 3e Communication. Stabilité des solutions ophtalmiques. Pharm Acta Helv 1969;44:348–55.Google Scholar
  4. 4.
    Porst H, Kny L. Zur Stabilität von Pilocarpinhydrochlorid in Augentropfen. Pharmazie 1985;40:23–9.Google Scholar
  5. 5.
    Chung P-H, Chin T-F, Lach JL. Kinetics of the hydrolysis of pilocarpine in aqueous solution. J Pharm Sci 1970;59:1300–6.Google Scholar
  6. 6.
    Nunes MA. Brochmann-Hanssen E. Hydrolysis and epimerization kinetics of pilocarpine in aqueous solution. J Pharm Sci 1974;63:716–21.Google Scholar
  7. 7.
    Drake MV, O'Donnell JJ, Polansky JR. Isopilocarpine binding to muscarinic cholinergic receptors. J Pharm Sci 1986;75:278–9.Google Scholar
  8. 8.
    Anderson RA, Cowle JB. Influence of pH on the effect of pilocarpine on aqueous dynamics. Br J Ophthalmol 1968;52:607–11.Google Scholar
  9. 9.
    Szepesi G, Gazdag M, Iváncsics R, Mihályfi K, Kovács P. Investigation of degradation mechanism of pilocarpine by HPLC. Pharmazie 1983;38:94–8.Google Scholar
  10. 10.
    Bundgaard H, Hansen SH. Hydrolysis and epimerization kinetics of pilocarpine in basic aqueous solution as determined by HPLC. Int J Pharm 1982;10:281–9.Google Scholar
  11. 11.
    Yoshioka S, Aso Y, Shibazaki T, Uchiyama M. Stability of pilocarpine ophthalmic formulations. Chem Pharm Bull 1986;34:4280–6.Google Scholar
  12. 12.
    Brochmann-Hanssen E, Schmid P, Benmaman JD. Quantitative determination of pilocarpine in ophthalmic solutions. J Pharm Sci 1965;54:783–4.Google Scholar
  13. 13.
    Durif C, Ribes M, Kister G, Puech A. Evaluation sémiquantitative rapide par CCM des acides pilo et isopilocarpiques dans les collyres à base de pilocarpine. Pharm Acta Helv 1986;61:135–8.Google Scholar
  14. 14.
    Neville GA, Hasan FB, Smith ICP. Quantitative analysis of degradation products in pilocarpine hydrochloride ophthalmic formulations. J Pharm Sci 1977;66:638–42.Google Scholar
  15. 15.
    Scott BS, Dunn DL, Dorsey ED. Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by UV spectrophotometry-polarimetry. J Pharm Sci 1981;70:1046–8.Google Scholar
  16. 16.
    Noordam A, Waliszewsky K, Olieman C, Maat L, Beyerman HC. Determination of the ophthalmic therapeutic pilocarpine and its degradation products by reversed-phase high-performance liquid chromatography. J Chromatogr 1978;153:271–3.Google Scholar
  17. 17.
    O'Donnell JJ, Sandman R, Drake MV. Measurement of pilocarpine and its degradation products by high-performance liquid chromatography. J Pharm Sci 1980;69:1096–7.Google Scholar
  18. 18.
    Kennedy JM, NcNamara PE. High-performance liquid chromatographic analysis of pilocarpine hydrochloride, isopilocarpine, pilocarpic acid and isopilocarpic acid in eye-drop preparations. J Chromatogr 1981;212:331–8.Google Scholar
  19. 19.
    Dunn DL, Thompson RE. Reversed-phase high-performance liquid chromatographic separation for pilocarpine and isopilocarpine using radial compression columns. J Chromatogr 1983;264:264–71.Google Scholar
  20. 20.
    Wood RW, Robinson JR. High-performance chromatographic determination of pilocarpine and pilocarpic acid in ocular tissues. Int J Pharm 1984;20:285–93.Google Scholar
  21. 21.
    Van Ackeren JL, Venable RM, Wainer IW. Separation and analysis of pilocarpine, isopilocarpine, and pilocarpic acid by reverse phase liquid chromatography: collaborative study. J Assoc Off Anal Chem 1984;67:924–6.Google Scholar
  22. 22.
    Ibrahim H, Boye T, Wermeille M, Gurny R, Buri P. Determination of pilocarpine by HPLC in presence of isopilocarpine and a pH-sensitive polymer in ophthalmic dispersions. J Pharm Biomed Anal 1987;5:379–82.Google Scholar
  23. 23.
    Vespalec R, Fiedorová M, Šubert J. Problems connected with HPLC separation of pilocarpine from its degradation products by means of silica gel and water-based mobile phase. Pharmazie 1988;43:689–91.Google Scholar
  24. 24.
    Durif C, Ribes M, Kister G. Puech A. Étude comparative du comportement des phases stationnaires en H.P.L.C. pour le dosage de la pilocarpine et de ses impuretés/produits de dégradation. Pharm Acta Helv 1988;63:294–8.Google Scholar
  25. 25.
    Durif C, Ribes M, Kister G, Puech A. Validation d'une technique HPLC de dosage de la pilocarpine et de ses impuretés/produits de dégradation. Pharm Acta Helv 1988;63:315–20.Google Scholar
  26. 26.
    Urbányi T, Piedmont A, Willis E, Manning G. Simultaneous determination of pilocarpine and isopilocarpine in pharmacetical preparations by liquid chromatography. J Pharm Sci 1976;65:257–60.Google Scholar
  27. 27.
    Dunn DL, Scott BS, Dorsey ED. Analysis of pilocarpine and isopilocarpine in ophthalmic solutions by normalphase high-performance liquid chromatography. J Pharm Sci 1981;70:446–9.Google Scholar
  28. 28.
    Mitra AK, Baustian CL, Mikkelson TJ. High-performance liquid chromatographic determination of pilocarpine in aqueous humor: derivatization by quartenarization of methylimidazole tertiary amine group. J Pharm Sci 1980;69:257–61.Google Scholar
  29. 29.
    Anonymous. Formularium der Nederlandse Apothekers, 's-Gravenhage: Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie. 1984:C59.Google Scholar
  30. 30.
    Boer Y, Cox HLM. Toelichting bij aanvulling 10 van het FNA [Comments to update 10 of the Formulary of Dutch Pharmacists]. Pharm Weekbl 1976;111:954–61.Google Scholar
  31. 31.
    Anonymous. British Pharmacopoeia 1988. London: Her Majesty's Stationary Office, 1988:684.Google Scholar
  32. 32.
    Anonymous. United States Pharmacopeia XXII. Rockville: United States Pharmacopeial Convention, 1989:1084.Google Scholar
  33. 33.
    Noordam A, Maat L, Beyerman HC. Quantitative determination of pilocarpine, isopilocarpine, pilocarpic acid, and isopilocarpic acid in clinical ophthalmic pilocarpine formulations by reversed-phase liquid chromatography. J Pharm Sci 1981;70:96–7.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1990

Authors and Affiliations

  • Paul F. M. Kuks
    • 1
  • Leo E. A. Weekers
    • 1
  • Pieter B. Goldhoorn
    • 1
  1. 1.Department of PharmacyTwenteborg HospitalSZ Almelothe Netherlands

Personalised recommendations