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.
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.
Su
Qi-Biao
QB
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, 74 Zhongshan Road, Section 2, Guangzhou, China.
He
Fan
F
Guan
Su
S
Lu
Yu-Jing
YJ
Gu
Lian-Quan
LQ
Huang
Zhi-Shu
ZS
Chen
Xiao
X
Huang
Min
M
Li
Chun-Guang
CG
Chowbay
Balram
B
Zhou
Shu-Feng
SF
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003959:Diamines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy*; D011804:Quinolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D019098:Telomerase / Q000037:antagonists & inhibitors*
D003959:Diamines; D004791:Enzyme Inhibitors; C521094:N'-(10H-indolo(3,2-b)quinolin-11-yl)-N,N-dimethylpropane-1,3-diamine; D011804:Quinolines; D019098:Telomerase