Determination of risperidone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study in Chinese volunteers

Abstract

This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25~50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%~9.09% and 1.56%~4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%~84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.

Solid‐phase extraction and analysis of paroxetine in human plasma by ultra performance liquid chromatography–electrospray ionization mass spectrometry

“…Diff erent analytical methods for determination of paroxetine as an antidepressant drug have been reported, including gas chromatography/mass spectrometry (GC-MS; Maurer et al, 2000), liquid chromatography (LC) with UV (Erk and Biryol, 2003), highperformance liquid chromatography-mass spectrometry (LC-MS) (Gutteck and Rentsch, 2003), gas chromatography (GC) with electro-capture detection (Lai et al, 2000), nitrogen-phosphorus detection (Lacassie et al, 2000) and negative ion chemical ionization mass spectrometry (Leis et al, 2001(Leis et al, , 2002, liquid chromatographic-tandem mass spectrometric (LC-MS/MS) (Massaroti et al, 2005;Jhee et al, 2007;Huang et al, 2008), with hydrophilic interaction (HILIC-MS/MS) (Naidong and Eerkes 2004), LC/MS with sonic spray ionization (SSI) (Shinozuka et al, 2006), liquid chromatographic-electrospray ionisation mass spectrometric (LC-ESI-MS) (Singh et al, 2004), solid-phase micro extraction and liquid chromatographic (SPME/LC-UV) (Silva et al, 2008), liquid chromatography with atmospheric pressure chemical ionization and tandem mass spectrometry (LC-APCI-MS/MS) (Chu and Metcalfe, 2007). Most of methods are liquid-liquid extraction while some methods are solid-phase extraction with longer analytical run time, higher concentration and high plasma processing volume.…”

Spectrophotometric Estimation of Aripiprazole in Tablets

“…The commonly used analytical techniques for the determination of risperidone are differential pulse polarography[1] chemiluminescence assay[2], HPLC-MS/MS[3], chiral chromatography[4], LC-MS[5], LC-tandem mass spectrometry[6], LC with electrochemical detection[78] LC with UV detection[9], LC with coulometric detection[10] and visible spectrophotometric method[11]. Colorimetric determination of drugs using the ferric chloride assay is simple and rapid.…”

Comparação da bioequivalência de duas formulações da risperidona

“…A análise de teor dos comprimidos não apresentou diferença estatisticamente significativa entre os medicamentos teste e referência, garantindo o teor declarado de 2 mg por comprimido dos produtos e, um lote Encontram-se, na literatura, vários métodos para a quantificação da RSP em matrizes biológicas como soro, plasma, cabelos, urina e saliva (Olesen e Linnet, 1997;Avenoso et al, 2000;Titier et al, 2002;Llerena et al, 2003;Titier et al, 2003;Flarakos et al, 2004;Moody et al, 2004;Riedel et al, 2005;Bhatt et al, 2006;Sattanathan et al 2006;Zhang et al, 2007a;Zhang et al, 2007b ;Bharathi et al, 2008;De Meulder et al, 2008;Huang et al, 2008). A urina não é muito utilizada para a quantificação da RSP e 9OH-RSP, principalmente em ensaios de bioequivalência, pois apenas cerca de 70% destas substâncias são eliminadas por esta via.…”