Determination of pKa values of fluphenazine analogs by reversed-phase high-performance liquid chromatography

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Sobczak-Kupiec Agnieszka, Beata Kaźmierska, P. Świątek, Izabela Muszalska-Kolos
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引用次数: 0

Abstract

Phenothiazine and its derivatives exhibit many properties. Hence they are the starting structures for many new potential drugs, biologically active compounds, dyes, etc. In this paper, we investigated a series of five fluphenazine analogs synthesized exhibiting inhibition of multidrug resistance (MDR) in tumor cells. During the drug discovery process, the determination of physicochemical properties of new compounds, such as dissociation constant values (pKa), is essential because it directly affects their pharmacokinetic profile. Thus, this study aimed to determine the pKa values of fluphenazine and its derivatives from the mobile phase pH dependence of the retention factor with the reverse phase liquid chromatographic method. Binary mixtures of phosphate buffer (pH 2.3-11.5) and acetonitrile (40-55%) in different percentages and the Gemini NX C18 column as the stationary phase were used in the tests. The pKa' values of fluphenazine derivatives at experimental concentrations of organic solvent were determined based on the obtained sigmoidal k curves as a function of pH. Then these values were extrapolated to 0% acetonitrile to obtain the actual pKa values. Moreover, a comparative evaluation of chromatographically obtained and computationally calculated pKa parameters was carried out.
反相高效液相色谱法测定氟奋乃嗪类似物的pKa值
吩噻嗪及其衍生物具有许多性质。因此,它们是许多潜在新药、生物活性化合物、染料等的起始结构。本文研究了一系列合成的五种对肿瘤细胞多药耐药性(MDR)具有抑制作用的氟吩嗪类似物。在药物发现过程中,测定新化合物的物理化学性质,如离解常数值(pKa),是至关重要的,因为它直接影响它们的药代动力学特征。因此,本研究旨在用反相液相色谱法从保留因子的流动相pH依赖性中确定氟奋乃嗪及其衍生物的pKa值。试验中使用不同百分比的磷酸盐缓冲液(pH 2.3-11.5)和乙腈(40-55%)的二元混合物,并使用Gemini NX C18柱作为固定相。根据所获得的作为pH函数的S形k曲线,测定了氟吩嗪衍生物在有机溶剂实验浓度下的pKa’值。然后将这些值外推到0%乙腈中,以获得实际的pKa值。此外,还对色谱法获得的pKa参数和计算得到的参数进行了比较评价。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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