High performance liquid chromatography with ultraviolet detection for the determination of SYUIQ-5, a novel telomerase inhibitor for cancer therapy: application to an enzyme kinetic study in rat liver microsomes.

Abstract

A sensitive assay for the determination of SYUIQ-5, a novel telomerase inhibitor and anti-tumor drug, in rat liver microsomes was developed by using high-performance liquid chromatography with ultraviolet detection. SYUIQ-5 was incubated in vitro with liver microsomes from rats pre-treated with control vehicle, beta-naphthofIavone, phenobarbital, 20% ethanol or dexamethasone. The analytes were extracted with diethyl ether and separated a C(18) 5-microm analytical column. Elution was conducted with 30 mM dipotassium hydrogen phosphate (pH 8.0)-methanol-triethylamine (30:70:0.05, v/v/v) at a flow-rate of 1.0 ml/min and the detection of UV absorbance was conducted at 278 nm. Intra-day and inter-day precision and accuracy of the method were within 10%. The mean analytical recoveries of SYUIQ-5 ranged from 78.8 to 95.3%. The linearity of the calibration curve was in the range of 1.0-80.0 microM. The lower limit of quantification (LOQ) was 1.0 microM. Kinetic analysis showed that beta-naphthofIavone and dexamethasone significantly induced SYUIQ-5 metabolism, suggesting that cytochrome P450 1A and 3A are the major contributor to SYUIQ-5 metabolism in rat liver microsomes.

• Authors: Qi-Biao Su, Fan He, Su Guan, Yu-Jing Lu, Lian-Quan Gu, Zhi-Shu Huang, Xiao Chen, Min Huang, Chun-Guang Li, Balram Chowbay, Shu-Feng Zhou
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 854 Issue 1-2 Pg. 332-7 (Jul 01 2007) ISSN: 1570-0232 [Print] Netherlands
• PMID: 17449337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diamines
• Enzyme Inhibitors
• N'-(10H-indolo(3,2-b)quinolin-11-yl)-N,N-dimethylpropane-1,3-diamine
• Quinolines
• Telomerase

Topics

• Animals
• Chromatography, High Pressure Liquid (methods)
• Diamines (pharmacokinetics, pharmacology, therapeutic use)
• Enzyme Inhibitors (pharmacokinetics, pharmacology, therapeutic use)
• Microsomes, Liver (drug effects, enzymology)
• Neoplasms (drug therapy)
• Quinolines (pharmacokinetics, pharmacology, therapeutic use)
• Rats
• Reproducibility of Results
• Sensitivity and Specificity
• Spectrophotometry, Ultraviolet (methods)
• Telomerase (antagonists & inhibitors)