Determination of Didanosine in Human Plasma and Its Application to a Bioequivalence Study
JIN Feng-dan1，CHEN Xiao-yan2，YU He-zhou3，AN Xiao-xia3，ZHONG Da-fang2
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1. Laboratory of Drug Metabolism and Pharmacokinetics，Shenyang Pharmaceutical University，Shenyang 110016，China； 2. Shanghai Institute of Materia Medica，Chinese Academy of Sciences，Shanghai 201203，China； 3.Northeast General Pharmaceutical Factory，Shenyang 110026，China
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History+
Received
Published
2005-07-11
2006-07-05
Issue Date
2006-07-05
Abstract
OBJECTIVE To develop a sensitive and specific LCMS/MS method for the determination of didanosine in human plasma and to study the bioequivalence of different formulations containing didanosine.METHODS After a simple protein precipitation using acetonitrile,the samples were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters of didanosine in two formulations were calculated by non-compartment analysis.RESULTS The linear calibration curves were obtained in the concentration range of 5.0～2 000 μg·L-1.The intra-and inter-day relative standard deviations(RSD) over the entire concentration range were less than 6%.Accuracy(RE) determined at three concentrations was within ±4%.Pharmacokinetic parameters for the reference formulation were obtained as follows: tmax was(0.65±0.30) h,ρmax was(1 052±353) μg·L-1,t1/2 was(1.53±0.38) h,AUC0～t was(1 628±479) μg·h·L-1.Pharmacokinetic parameters for the test formulation were obtained as follows: tmax was(0.47±0.13) h,ρmax was(1 090±531) μg·L-1,t1/2 was(1.44±0.46) h ,AUC0～t was(1 520±661) μg·h·L-1.The relative bioavailability of the test formulation to the reference was(95.8±20.8)%.CONCLUSION The method is sensitive,rapid,robust,and is proved to be suitable for bioequivalence evaluation of formulations containing didanosine.
JIN Feng-dn;CHEN Xio-yn;YU He-zhou;N Xio-xi;ZHONG D-fng.
Determination of Didanosine in Human Plasma and Its Application to a Bioequivalence Study [J]. Chinese Pharmaceutical Journal, 2006, 41(13): 1016-1019
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