A general HPLC–UV method for the quantitative determination of curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore in rat biomatrices

Abstract

Curcumin and its derivatives generally display favorable cytotoxic activities against a number of cancer cell types. We focus our rational antineoplastic drug design program on curcumin analogues containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore. Favorable outcomes from pharmacological screens of this series demanded further pharmacokinetic evaluations to determine their suitability as effective compounds in vivo. To allow such evaluations and to provide a general, sensitive, rapid and simple method for the analysis of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold, we developed an HPLC method with ultraviolet detection for their detection in various biological matrices of a relevant preclinical species, i.e. the rat. Our HPLC method is specific for the analysis of many members in this series in rat blood, plasma, serum and hepatic microsomes following liquid-liquid extraction with TBME (1:30, v/v). The assay procedure involves chromatographic separation on a Zorbax-Eclipse C-18 column under isocratic conditions with the mobile phase consisting of acetonitrile and ammonium acetate buffer (pH 5.0, 10 mM) in different ratios depending upon the compound. The method was validated for NC 2083 in rat serum and rat liver microsomes, a potential lead compound, to demonstrate its applicability. The standard curve was linear (r 2 ≥ 0.997) from 50 to 5000 ng/mL. Intra-and interday precision and accuracy of the method were within USFDA specified limits. The stability of NC 2083 was established in an auto-injector, on bench-top, during freeze-thaw cycles and longterm stability at −80 °C for 40 days. The method is suitable for a number of compounds containing the 1,5-diaryl-3-oxo-pentadienyl scaffold with divergent log P values with only minor adjustments in the buffer to acetonitrile ratio of the mobile phase.

High Sensitivity Method for Determination of Trace Curcumin in the Aqueous Phase

“…It has been reported that curcumin has many pharmacological functions, such as antioxygenation, antibiosis and antitumor [1][2][3] . Methods such as high-performance thin-layer chromatographic (HPTLC) [4][5][6][7] , high-performance liquid chromatography (HPLC) [8][9][10][11] , capillary electrophoresis with amperometric detection (CE-AD) 12 , matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOFMS) 13 , spectrofluorimetry 14,15 , liquid phase tandem mass spectrometry (LC-MS/MS) 16,17 , 1 H NMR 17 , resonance light scattering technique (RLS) 18 and spectrophotometry [19][20][21] have been employed to determine curcumin in a variety of matrixes. However, most of these methods have low sensitivity, need a large number of organic solvents or metal ions.…”

A highly selective nanocomposite based on MIP for curcumin trace levels quantification in food samples and human plasma following optimization by central composite design

“…Various role including antioxidant, anti-inflammatory, antibacterial, antiviral, anti-atherosclerotic, anti-arthriticagent and anticancer activities [16][17][18][19] are logical reasons for its extensive application and encourage researchers to design an accurate approach for preconcentration and quantification of curcumin in low level in complicated matrices. Several methods such as high-performance liquid chromatography [20][21][22], thin layer chromatography [23], UV-Vis spectrophotometry [24], HPTLC [25], 2-D flash liquid chromatography [26] and spectrofluorimetry [27,28] are applied for this regard. HPLC method compared to other techniques benefit from remarks like high reliability and efficiency and selectivity is appropriate for analyzing real samples with complex matrices, while for analytes with extremely low concentration a preliminarily preconcentration help the researchers to reduce the interference correspond to other constituents and simultaneously improve the performance of proposed method [29].…”

High‐sensitivity Determination of Curcumin in Human Urine Using Gemini Zwitterionic Surfactant as a Probe by Resonance Light Scattering Technique

“…Different techniques have been used for the analysis of curcumin, including UV-Vis spectrophotometry, high-performance thin-layer chromatography (HPTLC), and high-performance liquid chromatography (HPLC) (Bos et al, 2007;Mandal et al, 2008;Pozharitskaya et al, 2008;Wichitnithad et al, 2009;Singh et al, 2010). However, all these methods have the disadvantages of low sensitivity, multiple procedural steps and considerably high cost.…”