Determination of pKa and forced degradation of the indoloquinoline antimalarial compound cryptolepine hydrochloride.
Summary of "Determination of pKa and forced degradation of the indoloquinoline antimalarial compound cryptolepine hydrochloride."
The study was aimed at determining the acid dissociation constant of cryptolepine hydrochloride and its degradation under stressed conditions. The pKa was determined using buffers in the pH range 10.4-11.6 by spectrophotometry at controlled measurement temperature (20 ± 0.5°C). The stability of the compound was investigated under various stressed conditions including neutral, acid, alkaline, light, dry heat and oxidation at different temperatures. Degradation products were analysed by HPLC. The calculated pKa values (uncorrected and corrected for ionic strength) were 11.09 ± 0.03 and 10.99 ± 0.05, respectively. A graphical approach yielded an uncorrected pKa value of 11.07. Degradation of the compound in water, 0.1 M HCl, 0.1 M NaOH and 3% hydrogen peroxide followed a first order reaction. With proper temperature control and maintenance of uniform ionic strength, a reproducible pKa of cryptolepine is obtainable by spectrophotometry. The compound was found to be highly susceptible to oxidation and relatively stable in neutral and acidic conditions but less so in a basic medium. There were no significant changes in concentration of samples exposed to light and dry heat at 60°C over the study period.
Affiliation
School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland , Auckland , New Zealand.
Journal Details
This article was published in the following journal.
Name: Pharmaceutical development and technology
ISSN: 1097-9867
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22436019
- DOI: http://dx.doi.org/10.3109/10837450.2012.668554
Medical and Biotech [MESH] Definitions
Forced Expiratory Flow Rates
The rate of airflow measured during a FORCED VITAL CAPACITY determination.
Forced Expiratory Volume
Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity.
Chloroguanide
A biguanide compound which has little antimalarial activity until metabolized in the body to the active antimalarial agent cycloguanil. The usefulness of proguanil is limited by the rapid development of drug resistance by the malarial parasite. The hydrochloride is used for the casual prophylaxis of falciparum malaria, to suppress other forms of malaria, and to reduce transmission of infection (From Martindale, The Extra Pharmacopoeia, 30th ed, p405)
Peak Expiratory Flow Rate
Measurement of the maximum rate of airflow attained during a FORCED VITAL CAPACITY determination. Common abbreviations are PEFR and PFR.
Maximal Expiratory Flow Rate
The airflow rate measured during the first liter expired after the first 200 ml have been exhausted during a FORCED VITAL CAPACITY determination. Common abbreviations are MEFR, FEF 200-1200, and FEF 0.2-1.2.
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