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Arzneimittelforschung 2007; 57(7): 455-461
DOI: 10.1055/s-0031-1296631
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Determination of Paroxetine in Plasma by Liquid Chromatography Coupled to Tandem Mass Spectrometry for Pharmacokinetic and Bio equivalence Studies

Ok Hwa Jhee
1   Department of Practical Arts Education, Gongju National University of Education, Gongju, Chungnam, South Korea
,
Hee Kyoung Seo
2   Department of Pharmacology & Institute of Biomedical Sciences, College of Medicine, Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea
,
Min Ho Lee
3   Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, South Korea
,
Yong Cheol Jeon
3   Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, South Korea
,
Leslie M. Shaw
4   Department of Pathology & Lab Medicine, College of Medicine, University of Pennsylvania, Philadelphia, PA, USA
,
Seung Hoon Lee
5   Biologics Team, Biologics Headquarters, Korea Food and Drug Administration, Seoul, South Korea
,
Yeon Hur
6   Pharmacokinetic Laboratory, Bio-Mediang Co., Gyunggi-Do, South Korea
,
Kwang-Hyun Kim
6   Pharmacokinetic Laboratory, Bio-Mediang Co., Gyunggi-Do, South Korea
,
Heon-Soo Lee
6   Pharmacokinetic Laboratory, Bio-Mediang Co., Gyunggi-Do, South Korea
,
Seo Eun Lee
7   Department of Physiology, College of Medicine, Hanyang University, Seoul, South Korea
,
Ju Seop Kang
2   Department of Pharmacology & Institute of Biomedical Sciences, College of Medicine, Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea
› Author Affiliations
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Publication History

Publication Date:
21 December 2011 (online)

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Abstract

A rapid and validated liquid chromatography coupled to tandem mass spectro-metric 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, m/z 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.

Key words

Antidepressants - CAS 61869-08-7 - Paroxetine, bioequivalence study, liquid chromatography/ tandem mass spectrometry, pharmacokinetics