Determination of paroxetine in plasma by liquid chromatography coupled to tandem mass spectrometry for pharmacokinetic and bioequivalence studies.
A rapid and validated liquid chromatography coupled to tandem mass spectrometric method (LC-MS-MS) has been developed and applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean volunteers. The procedure involves a liquid-liquid extraction of paroxetine (CAS 61869-08-7) and fluoxetine (internal standard, CAS 54910-89-3) with ether/methyl chloride (7:3, v/v) and separated by LC equipped with C18 column using acetonitrile: 5 mmol/L ammonium formate (4:3, v/v) as mobile phase. Detection is carried out on an API 2000 MS system by multiple reactions monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved by MS-MS analysis, mlz 330.0-->192.0 and m/ z 310-->148 for paroxetine and fluoxetine, respectively. The method has a total run time of 1.5 min and was linear over a working range of 0.05-20 ng/mL and the lower limit of quantification was 0.05 ng/ mL. No endogenous compounds were found to interfere with the analysis. The inter-day and intra-day accuracy was in the ranges of 102.69-107.79% and 102.07-109.57%, respectively and precision of inter-day and intra-day expressed as relative standard deviation were 1.86-9.99% and 1.52-6.28%, respectively. The validation of this method on linearity, specificity, accuracy, precision as well as applicability to pharmacokinetic and bioequivalence studies by analysis of blood samples taken up to 72 h after oral administration of 20 mg of paroxetine in 24 healthy volunteers were found to be good performance.
Jhee
Ok Hwa
OH
Department of Practical Arts Education, Gongju National University of Education, Gongju, Chungnam, South Korea.
Seo
Hee Kyoung
HK
Lee
Min Ho
MH
Jeon
Yong Cheol
YC
Shaw
Leslie M
LM
Lee
Seung Hoon
SH
Hur
Yeon
Y
Kim
Kwang-Hyun
KH
Lee
Heon-Soo
HS
Lee
Seo Eun
SE
Kang
Ju Seop
JS
D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D006801:Humans; D017374:Paroxetine / Q000097:blood* / Q000493:pharmacokinetics*; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency