Publications (2)2.97 Total impact
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Article: Nature of the main contaminant in the drug primaquine diphosphate: SFC and SFC-MS methods of analysis.
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ABSTRACT: The drug primaquine diphosphate is used for causative treatment of malaria. Using HPLC-MS and GC-MS, this research group was previously able to show that the main contaminant of primaquine is the positional isomer quinocide [I. Brondz, D. Mantzilas, U. Klein, D. Ekeberg, E. Hvattum, M.N. Lebedeva, F.S. Mikhailitsyn, G.D. Soulimanov, J. Roe, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 800 (2004) 211-223; I. Brondz, U. Klein, D. Ekeberg, D. Mantzilas, E. Hvattum, H. Schultz, F. S. Mikhailitsyn, Asian J. Chem. 17 (2005) 1678-1688]. Primaquine and quinocide are highly toxic substances which can have a number of side effects upon use in medical treatment. A standard for quinocide is not typically commercially available. In the present work, supercritical fluid chromatography-mass spectrometry (SFC-MS) with two different columns was used to achieve a shorter analysis time for the separation between the positional isomers quinocide and primaquine in primaquine diphosphate and to elucidate additional information about differences in their MS fragmentation. Unlike using HPLC-MS, it was possible to achieve the differential fragmentation of positional isomers at branching points using the SFC-MS technique. The desired short analysis time was achieved using SFC equipped with a Discovery HS F5 column and the differential fragmentation of positional isomers during SFC-MS provides information on the differences in the structure of these substances. Using a Chiralpak AD-H chiral column, it was possible to resolve the enantiomers in primaquine and separate quinocide from those enantiomers.Journal of Pharmaceutical and Biomedical Analysis 03/2007; 43(3):937-44. · 2.97 Impact Factor -
Article: Separation of the positional isomer quinocide from the anti-malaria drug primaquine using a Discovery HS-F5 HPLC column
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ABSTRACT: Malaria is one of the most deadly diseases on earth with an estimated death rate of up to 2.7 million humans per year. The drug primaquine di-phosphate is used for causative treatment of this infection. Using HPLC equipped with a chiral column and HPLC-MS equipped with a reverse-phase column, we were able to show that the main contaminant of primaquine is the positional isomer quinocide [1]. Using GC, GC-MS we supported previously results and were able to work out the detailed fragmentation map for primaquine and quinocide and to compare the fragmentation [2]. HPLC is the main method in the Pharmacopeias and used in pharmaceutical industries. However, by HPLC, on the columns used [1], the isomers of primaquine were not adequately separated and therefore it is difficult to quantify the highly toxic contaminant, quinocide. The base line separation is a request in Pharmacopoeia. A novel method for separation of quinocide from primaquine was developed on the HPLC Discovery HS-F5 column resulting in baseline resolution suitable for quantification. Baseline separation was achieved isocratic by varying the buffer proportion in the acetonitrile mobile phase at a flow rate of 1.0 ml/min. The mobile phase composition finally chosen was acetonitrile/20 mM ammonium acetate in distilled water, pH 7.0, 50/50. The analytes were detected at 268 nm with reference at 300 nm. SFC was also tested as an alternative to HPLC [3]. The Discovery HS-F5 column has advantages in separation on HPLC and SFC over the other columns tested to date. In the experiments with SFC it was possible to get more realistic quantitative results than in HPLC, these results are supporting the previous data of toxicological tests [1]. By using SFC it was also possible to reduce the time for analysis.research trends. 01/2005; 1:77-81.
