Brondz Ilia, Ekeberg Dag, Bell David S, Annino Amy R, Hustad Jan Arild, Svendsen Robert, Vlachos Vaso, Oakley Paul, Langley G John, Mohini Thite, Amaury Cazenave-Gassiot, Mikhalitsyn Felix
University of Life Sciences, Department of Chemistry, Biotechnology and Food Science, As, Norway.
J Pharm Biomed Anal. 2007 Feb 19;43(3):937-44. doi: 10.1016/j.jpba.2006.09.017. Epub 2006 Oct 31.
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.
磷酸伯氨喹用于疟疾的病因治疗。该研究小组此前利用高效液相色谱 - 质谱联用（HPLC-MS）和气相色谱 - 质谱联用（GC-MS）技术，证实了伯氨喹的主要污染物是位置异构体喹诺酮[I. 布隆兹、D. 曼齐拉斯、U. 克莱因、D. 埃克贝里、E. 赫瓦图姆、M.N. 列别杰娃、F.S. 米哈伊利琴、G.D. 苏利马诺夫、J. 罗，《色谱杂志B：分析技术、生物医学与生命科学》800（2004）211 - 223；I. 布隆兹、U. 克莱因、D. 埃克贝里、D. 曼齐拉斯、E. 赫瓦图姆、H. 舒尔茨、F.S. 米哈伊利琴，《亚洲化学杂志》17（2005）1678 - 1688]。伯氨喹和喹诺酮都是剧毒物质，用于医学治疗时可能会产生多种副作用。喹诺酮标准品通常没有商业供应。在本研究中，使用配备两种不同色谱柱的超临界流体色谱 - 质谱联用（SFC-MS）技术，以缩短磷酸伯氨喹中位置异构体喹诺酮和伯氨喹之间的分离分析时间，并阐明它们在质谱碎裂方面差异的更多信息。与使用HPLC-MS不同，利用SFC-MS技术可以在分支点实现位置异构体的差异碎裂。使用配备Discovery HS F5色谱柱的SFC实现了所需的短分析时间，并且SFC-MS过程中位置异构体的差异碎裂提供了这些物质结构差异的信息。使用Chiralpak AD-H手性色谱柱，可以分离伯氨喹中的对映体，并将喹诺酮与这些对映体分开。
