Simultaneous determination of N-butyramide-tacrine and tacrine in mouse plasma and brain homogenate by high-performance liquid chromatography with a simple gradient solvent system.
A novel reversed-phase HPLC method was developed for the simultaneous determination of tacrine (THA) and the newly synthesized prodrug (N-butyramide-THA, BTHA) in mouse plasma and brain homogenate. The assay involves deproteinisation and subsequent detection at 240 nm with a gradient solvent system. Retention times were 18.5 and 9.3 min for BTHA and THA, respectively. Average recoveries for the analytes were 80.7% (BTHA) and 76.6% (THA) from plasma, and 75.0% (BTHA) and 68.4% (THA) from brain homogenate. Linear responses were observed over a wide range (0.25-20 microg/ml for BTHA in plasma and in brain homogenate, 0.025-20 microg/ml for THA in both matrices). Both BTHA and THA degraded from the prodrug can be detected even 12 h after intravenous administration of BTHA, indicating that BTHA is a promising prodrug for brain targeting.
Jiang
Y
Y
No. 17, Section 3, Renmin Nan Road, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Zhang
Y
Y
Zhang
Z R
ZR
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002138:Calibration; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051379:Mice; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry*; D013619:Tacrine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; C482141:N-butyramide-tacrine; D012997:Solvents; D013619:Tacrine