TITLE:
The Technology for Preparation of Generic (Monoenantiomeric) Antimalarial Drug Primaquine by Using Supercritical Fluid Chromatography. Separation of Primaquine from Quinocide: Simultaneous Resolution of the Enantiomers of Primaquine and Their Separation from Quinocide in One Run
AUTHORS:
Ilia Brondz, Anton Brondz
KEYWORDS:
Primaquine; Quinocide; High Resolution Isomer Column; Monoenantiomeric Primaquine; Malaria; SFC; New Technology Column HRIC
JOURNAL NAME:
American Journal of Analytical Chemistry,
Vol.3 No.12A,
December
31,
2012
ABSTRACT: Malaria is one of the most
harmful diseases on the globe. According to the World Health Organization
(WHO), several million people die every year from malaria, and most of them are
children. Hundreds of millions of fresh cases of ma- laria are
registered by the WHO every year, and more than one-third of the earth’s
population lives in malaria-endemic areas. Primaquine is an important
antimalarial drug because it has gametocytocidal properties and prevents
relapse in most cases. However, primaquine is a highly toxic substance,
especially to the Negroid race (in Africa, Australia and North, Latin and South
America) and some others. Negroid male children are most vulnerable to the
toxic effects of primaquine. The toxicity of primaquine can be enhanced in
mixtures with other antimalarial drugs. In the present study, unprocessed
primaquine and primaquine tablets highly contaminated with quinocide (I.
Brondz, Historical Overview of Chromatography and Related Techniques in
Analysis of Antimalarial Drug Primaquine (Editor I. Brondz), Nova Sci- ence
Publishers, Inc. (2011) ISSN 978-1-61761-944-1) are discussed versus
monoenantiomeric primaquine as a drug. The contamination of primaquine with
quinocide enhances the toxicity of primaquine by additive or synergistic
action. The use of contaminated primaquine can be harmful. Development of a
useful antimalarial vaccine can take a decade or longer. This paper describes
the possibility of preparing antimalarial generic monoenantiomeric primaquine,
free of both quinocide contamination and the ineffective enantiomer of
primaquine, using fractionation by supercritical fluid chromatography equipped with a new experimental High Resolution Isomer
Column (HRIC). By this approach, it is pos- sible to produce a significant amount of pharmacologically active
enantiomer of primaquine at relatively low cost for a broad range of patients
sensitive to contaminated primaquine. Leading pharmacopoeias should no longer
deny the pre- sence of the toxic contaminant quinocide in relatively high
concentrations in unprocessed primaquine and in prima- quine tablets. New
standards for antimalarial primaquine diphosphate tablets must be adopted in
pharmacopoeias and by the pharmaceutical industry.