698
A. El-Gindy / Il Farmaco 60 (2005) 689–699
pound concentration present in pharmaceutical product, to
give accurate, precise and linear results. The calibration range
4. Conclusion
The proposed HPLC method provides simple, accurate and
reproducible quantitative analysis for the determination of OL,
OB, their degradation products (DA, CA), MP and PP in phar-
maceutical products, without any interference from the excipi-
ents. It was found that OL and OB are rapidly degraded in
alkaline medium, while they are more stable in acidic medium.
The most stability of OL and OB was found to be at pH 4.0.
3.5.4. Detection and quantitation limits
According to ICH recommendations [25], the approach
based on the S.D. of the response and the slope was used for
determining the detection and quantitation limits. The theo-
retical values were assessed practically and are given in
References
3.5.5. Selectivity
Method selectivity was achieved by preparing different
laboratory-prepared mixtures of OL, DA, MP, PP or OB, CA,
MP, PP at various concentrations within the linearity range.
The laboratory-prepared mixtures were analyzed. Satisfac-
high selectivity of the proposed method for determination of
the studied compounds.
The proposed method is highly selective towards OL, OB,
MP, PP, DA and CA. Regarding 2-[2-(diethylamino)ethoxy]
ethyl alcohol (EA) and 4-(diethylamino)-2-butynyl alcohol
(BA), it is assumed that their ultraviolet absorption charac-
teristics are relatively low to be detected by the assay condi-
tions used in this work.
[1] S.C. Sweetman, in: Martindale—The Complete Drug Reference, 33rd
ed, Pharmaceutical Press, London, 2002, pp. 1096.
[2] C. Knopp, W. Korsatko, Determination of oxeladin citrate in com-
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[3] F.A. Mohamed, A.-M. Mohamed, H.A. Mohamed, S.A. Hussein,
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[6] C. Lartigue-Mattei, M.J. Galmier, J.L. Chabard, E. Beyssac,
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3.5.6. Accuracy
[7] E. Van Gyseghem, S. Van Hemelryck, M. Daszykowski, F. Questier,
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This study was performed by addition of known amounts
of OL, OB, their degradation products (DA, CA), MP and PP
to a known concentration of the commercial pharmaceutical
products (standard addition method). The resulting mixtures
were assayed and the results obtained for added compounds
were compared with the expected results. The excellent recov-
the good accuracy of the proposed methods.
Extreme degradation of OL and OB in aqueous solution
was achieved by acid and alkaline hydrolysis. No peaks inter-
fering with the elution of OL, OB, MP, and PP were observed
in both cases.
The influence of the commonly used syrup, capsule and
tablet excipients (glycerin, propylene glycol, sucrose, sorbi-
tol, ethanol, citric acid, sodium citrate, sunset yellow, lac-
tose, starch, magnesium stearate, talc, microcrystalline cellu-
lose) was investigated before the determination of the studied
compounds in pharmaceutical products. No interference could
be observed with the proposed methods.
[8] M.J. O’Neil, A. Smith, P.E. Heckelman, The Merck Index, An Ency-
clopedia of Chemicals, Drugs and Biologicals, 13th ed, Merck, Inc.,
Whitehouse Station, NJ, USA, 2001 (p. 1245).
[9] The United States Pharmacopeia 27, in: The National Formulary 22,
United States Pharmacopeial Convention, Inc., 2004, pp. 1373–1375.
[10] British Pharmacopoeia, in: The Stationery Office, London, 2003,
pp. 1397–2538.
[11] in: European Pharmacopoeia, Fourth ed, Council of Europe, Stras-
bourg, France, 2002, pp. 1689.
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and use of octakis(2,3-di-O-methyl-6-O-sulfo)-c-cyclodextrin,
a
novel, single-isomer, chiral resolving agent in low-pH background
electrolytes, Electrophoresis 24 (2003) 351–362.
[13] Application—Oxybutynin chiral separation, Chrom. Tech. Applica-
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3.5.7. Robustness
[15] T.A. Walker, The chiral separation of oxybutynin enantiomers using
an ovomucoid column, J. Liquid Chromatogr. Related Technol. 23
(2000) 841–853.
Variation of the organic strength of the mobile phase
by 2% did not have a significant effect on chromatographic
resolution of the studied compounds.
[16] E. Miyamoto, Y. Demizu, Y. Murata, Y. Yamada, S. Kawashima,
H. Kontani, T. Sakai, High-performance liquid-chromatographic
preparation of oxybutynin enantiomers on a chiral stationary phase, J.
Chromatogr. A. 653 (1993) 135–137.
3.5.8. Stability
The studied compound solutions in mobile phase exhib-
ited no chromatographic changes for 3 h when kept at room
temperature, and for 8 h when stored refrigerated at 5 °C.
[17] E. Miyamoto, S. Kawashima, Y. Murata, Y. Yamada, Y. Demizu,
H. Kontani, T. Sakai, Physicochemical properties of oxybutynin,
Analyst 119 (1994) 1489–1492.