Validation of an HPLC Method for the Simultaneous Quantification of Metabolic Reaction Products Catalysed by CYP2C11 Enzymes in Rat Liver Microsomes: In Vitro Inhibitory Effect of Salicylic Acid on CYP2C11 Enzyme

The inhibitory effect of new chemical entities on rat liver P450 marker activities was investigated in a functional approach towards drug development. Treatment of colorectal cancer (CRC) and chemoprevention using salicylic acid has gained a lot of attention, mainly in the prevention of the onset of...

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Published in:	Molecules (Basel, Switzerland) Switzerland), 2019-11, Vol.24 (23), p.4294
Main Authors:	Salhab, Hassan, Naughton, Declan P, Barker, James
Format:	Article
Language:	eng
Subjects:	Animals Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors Aryl Hydrocarbon Hydroxylases - chemistry Calibration Catalysis Chromatography Chromatography, High Pressure Liquid Colon Colon cancer Colorectal carcinoma Cytochrome Cytochrome P-450 Enzyme Inhibitors - chemistry Cytochrome P-450 Enzyme Inhibitors - pharmacology Cytochrome P450 Family 2 - antagonists & inhibitors Cytochrome P450 Family 2 - chemistry Drug Development Drugs Enzymatic activity Enzyme activity Enzymes Fatty acids High performance liquid chromatography Humans Liquid chromatography Liver Liver - drug effects Liver - enzymology Metabolism Metabolites Microsomes Quantitation Rats Reaction products Salicylic acid Salicylic Acid - chemistry Salicylic Acid - pharmacology Standard deviation Steroid 16-alpha-Hydroxylase - antagonists & inhibitors Steroid 16-alpha-Hydroxylase - chemistry Substrates Testosterone Toxicity
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Summary:	The inhibitory effect of new chemical entities on rat liver P450 marker activities was investigated in a functional approach towards drug development. Treatment of colorectal cancer (CRC) and chemoprevention using salicylic acid has gained a lot of attention, mainly in the prevention of the onset of colon cancer. Thus, an in vitro inhibitory effect of salicylic acid on rat CYP2C11 activity was examined by using high performance liquid chromatography (HPLC). High performance liquid chromatography analysis of a CYP2C11 assay was developed on a reversed phase C column (SUPELCO 25 cm × 4.6 mm × 5 µm) at 243 nm using 32% phosphate buffer (pH 3.36) and 68% methanol as a mobile phase. The CYP2C11 assay showed good linearity for all components (R > 0.999). Substrates and metabolites were found to be stable for up to 72 hours. Additionally, the method demonstrated good reproducibility, intra- and inter-day precision (
ISSN:	1420-3049 1420-3049