Published:Journal of Chromatographic Science,
ISSN 0021-9665 Volume 45,
Number 2, February 2007, pp.63-69
Separation, Characterization, and Quantitation
of Process-Related Substances of the Anti-Hypertensive Drug Doxazosin
Mesylate by Reversed-Phase LC with PDA and ESI-MS as Detectors
R. Nageswara Rao[1], D. Nagaraju[1], A.K. Das[2],
and Nivedita Jena[2]
[1]HPLC/UV Group, Division of Analytical Chemistry, Discovery
Laboratory and
[2]Specialty Gas-based Chemicals and Processes Division, Indian
Institute of Chemical Technology, Hyderabad – 50 0007, India
A simple and rapid reversed-phase liquid chromatography
(LC) method with photodiode array (PDA) and electrospray ionization
(ESI)–mass spectrometry (MS) as detectors was developed
and validated to separate, identify, and quantitate the related
substances of Doxazosin mesylate (DXZN) for monitoring the reactions
involved during process development. The high-performance liquid
chromatography profiles of related-substances of DXZN are used
as fingerprints to follow the procedures used in the manufacturing
units. The separation is accomplished on an Inertsil ODS-3 column
with acetonitrile–ammonium acetate (10mM, pH 4.0) as the
mobile phase, using a gradient elution mode and monitoring the
eluents by a photodiode array detector at 265 nm at ambient temperature.
LC–ESI-MS–MS is used to identify the additional impurities
formed during the synthesis. The identified impurities were synthesized
and characterized by UV, Fourier transform-IR, 1H NMR, and MS
data. The detection limits for the impurities are 0.74 –
4.14 ¥ 10–9g , and the method is found to be suitable
not only for the monitoring of synthetic reactions, but also for
quality assurance of DXZN in bulk drugs and formulations.
Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
This
article is available in its entirety by fax for $4.00 per
page.
Visa or MasterCard accepted.
To
order electronicallyclick here or call: 847-647-2900 ext. 1323 or fax request to: 847-647-1155.
Please
indicate JCS volume and issue along with
page numbers.
