TITLE:
Supercritical Fluid Chromatography—Mass Spectrometry (SFC-MS) and MALDI-TOF-MS of Heterocyclic Compounds with Trivalent and Pentavalent Nitrogen in Cough Relief Medical Forms Tuxi and Cosylan
AUTHORS:
Ilia Brondz, Anton Brondz
KEYWORDS:
SFC; Trivalent Nitrogen; Pentavalent Nitrogen; Pholcodine-N-oxide; Pholcodine-N, N’-dioxide; Morphine; Cosylan; Tuxi; Tuxi Forte; Tuxidrin
JOURNAL NAME:
American Journal of Analytical Chemistry,
Vol.3 No.12A,
December
31,
2012
ABSTRACT: Alkaloids are natural, semisynthetic or synthetic
organic compounds, normally polar with basic chemical properties and containing
at least one nitrogen atom in a heterocyclic ring. Some synthetic or
semisynthetic substances resemble the alkaloid architecture. Trivalent nitrogen
in these substances is normal; however, some natural and semisynthetic alkaloids
have pentavalent nitrogen. The drug pholcodine is a derivative of morphine. Pholcodine
has very little addiction- developing effect. It is a semisynthetic
alkaloid that was first synthesized in 1950 by Chabrier et al. Pholcodine possesses antitussive (cough relief) properties
similar to codeine, morphine and ethylmorphine. The drug was used in liquid
formulations as Tuxi and Tuxi Forte, and it is in present use in Tuxidrin as
liquid mixture and in tablet form. Pholcodine is an Active Pharmacological
Ingredient (API) in tablets and liquid mixtures. Leiras International and Weifa
in Norway manufacture medical forms with pholcodine. Several impurities in
pholcodine were described by J. Roe in 1997 and by Denk et al. in 2000 and 2002. In addition, several degradation products
may be formed in liquid formulations under storage. Some of these products are
related not to the original production of pholcodine but rather to its
oxidation under storage. The appearance of
degradation products strongly depends on the storage temperature and pH of the
liquid phase. Pholcodine-N-oxide and pholcodine-N,N’-dioxide
are among the degradation (oxidation) products; pholcodine can also degrade to
morphine. There is little information about the toxicity of the N-oxide and no
information on the N,N’-di- oxide of pholcodine. In this study, the fact that morphine is
generated during the storage of formulations containing pholcodine is
presented. Another antitussive mixture under the name Cosylan was analyzed to
examine the oxidation of ethylmorphine to ethylmorphine-N-oxide. Ethylmorphine
is the API in Cosylan.