[Bioequivalence of donepezil capsule and tablet in human].
OBJECTIVE
To develop an HPLC-MS assay for determination of donepezil in human plasma and to investigate the pharmacokinetics and bioequivalence of donepezil capsule in healthy volunteers.


METHODS
A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 5 mg dose of either capsule or tablet was administered to each volunteer. After spiked with the internal standard (phenoprolamine) and treated with saturated sodium bicarbonate, plasma was extracted with ethyl acetate and separated with a C18 reversed phase column. LC-ESIMS was used in the selected ion monitoring (SIM) mode with target ions at m/z 380 for donepezil and m/z 344 for phenoprolamine. The fragmentor voltage was 120 V. The main pharmacokinetic parameters of donepezil and the bioequivalence of its two preparations were calculated.


RESULTS
The main pharmacokinetic parameters T1/2, Tmax and Cmax were (63 +/- 10) h, (3.3 +/- 0.4) h and (8.5 +/- 0.4) microgram.L-1 for the capsule; (57 +/- 9) h, (3.4 +/- 1.0) h and (8.1 +/- 1.0) microgram.L-1 for the tablet, respectively. The relative bioavailability of the donepezil capsule was 102% +/- 11%.


CONCLUSIONS
The assay was shown to be sensitive, accurate and convenient. The two preparations of donepezil were bioequivalent.
Hao
Xin-yu
XY
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Ding
Li
L
Li
Li-ming
LM
Bian
Xiao-jie
XJ
Zhang
Sheng-qiang
SQ
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets / Q000737:chemistry; D013810:Therapeutic Equivalency
D002214:Capsules; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D013607:Tablets; D000077265:Donepezil