Simultaneous determination of galantamine, rivastigmine and NAP 226-90 in plasma by MEKC and its application in Alzheimer's disease.
A simple and sensitive MEKC with UV detection was developed and validated for the simultaneous determination of acetylcholinesterase inhibitors including galantamine, rivastigmine and major metabolite NAP 226-90 in plasma. A sample pretreatment by liquid-liquid extraction with diethylether and subsequent quantification by MEKC was used. The optimum separation for these analytes was achieved in <10 min at 25 degrees C with a fused-silica capillary column of 30.2 cm x 50 microm id (effective length 20 cm) and a run buffer containing 25 mM Tris buffer (pH 5.0) with 160 mM sodium octanesulfonate, 20% ACN and 0.01% PVP as a dynamic coating to reduce analytes' interaction with the capillary wall. For sensitivity consideration regarding the determination of linearity, LOD, quantitation and monitoring drugs concentration in patients, the detection wavelengths for galantamine or rivastigmine and NAP 226-90 were set at 214 or 200 nm, respectively. One male volunteer (26-year-old) was orally administered a single dose of 4.5 mg rivastigmine (Exelon, Novartis) in capsule, and blood samples were drawn over a 12 h period for concentration-time profile study. The method was also successfully applied for monitoring galantamine or rivastigmine and its metabolite NAP 226-90 in 11 Alzheimer's disease patients' plasma after oral administration of the commercial products Reminyl (8 mg galantamine/capsule) or Exelon (3 mg rivastigmine/capsule), respectively.
Hsieh
Ya-Hui
YH
Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yang
Yuan-Han
YH
Yeh
Hsin-Hua
HH
Lin
Ping-Chih
PC
Chen
Su-Hwei
SH
D000328:Adult; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy*; D001596:Benzylamines / Q000097:blood*; D002021:Buffers; D002800:Cholinesterase Inhibitors / Q000097:blood; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005702:Galantamine / Q000097:blood*; D006801:Humans; D008297:Male; D010627:Phenethylamines; D010636:Phenols / Q000097:blood*; D048448:Phenylcarbamates / Q000097:blood*; D010756:Phosphoric Acids / Q000737:chemistry; D015203:Reproducibility of Results; D000068836:Rivastigmine; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
C494046:3-(1-dimethylaminoethyl)phenol; D001596:Benzylamines; D002021:Buffers; D002800:Cholinesterase Inhibitors; D010627:Phenethylamines; D010636:Phenols; D048448:Phenylcarbamates; D010756:Phosphoric Acids; D012997:Solvents; D013501:Surface-Active Agents; D005702:Galantamine; D000068836:Rivastigmine