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LC/ESI-MS/MS determination of domperidone in human plasma

Hou Yan-ning

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Abstract

Objective:To develop a rapid,sensitive,and specific LC/electrospray ionization(ESI)-MS/MS meth- od for determination of domperidone in human plasma.Methods:The analyte was treated by methanol precipitation to remove protein component from human plasma,then separated on a Phenomenex Gimini C_(18) column(2.00 mm× 50 mm,5μm).The mobile phase consisted of methanol-water(40:60,v/v,containing 0.3 % acetic acid),at a flow rate of 0.2 mL·min~(-1).A linear trap mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode.In multipole ion reaction monitoring(MRM)mode,the ion reac- tion combinations of m/z 426→m/z 175 and ra/z 379→m/z 264 were used to qualify domperidone and internal standard(ambroxol),respectively.Results:Chromatograms showed no endogenous interference peaks with the re- spective blank human plasma samples.Each analysis was completed with in 2 min.The calibration was linear in the concentration range of 0.3-100 ng·mL~(-1),and quantitative limit was 0.3 ng·mL~(-1).The intra-day and inter- day RSDs were less than 7.1% and 13.3%,respectively.The accuracy determined as relative error was less than 5.4%.Conclusion:The method is proved to be suitable for clinical investigation of pharmacokinetics of therapeutic dose of domperidone,which offers advantages of specificity,quickness,and sensitivity over the previously reported methods.

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Objective:To develop a rapid,sensitive,and specific LC/electrospray ionization(ESI)-MS/MS meth- od for determination of domperidone in human plasma.Methods:The analyte was treated by methanol precipitation to remove protein component from human plasma,then separated on a Phenomenex Gimini C_(18) column(2.00 mm× 50 mm,5μm).The mobile phase consisted of methanol-water(40:60,v/v,containing 0.3 % acetic acid),at a flow rate of 0.2 mL·min~(-1).A linear trap mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode.In multipole ion reaction monitoring(MRM)mode,the ion reac- tion combinations of m/z 426→m/z 175 and ra/z 379→m/z 264 were used to qualify domperidone and internal standard(ambroxol),respectively.Results:Chromatograms showed no endogenous interference peaks with the re- spective blank human plasma samples.Each analysis was completed with in 2 min.The calibration was linear in the concentration range of 0.3-100 ng·mL~(-1),and quantitative limit was 0.3 ng·mL~(-1).The intra-day and inter- day RSDs were less than 7.1% and 13.3%,respectively.The accuracy determined as relative error was less than 5.4%.Conclusion:The method is proved to be suitable for clinical investigation of pharmacokinetics of therapeutic dose of domperidone,which offers advantages of specificity,quickness,and sensitivity over the previously reported methods.

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Available abstract

Objective:To develop a rapid,sensitive,and specific LC/electrospray ionization(ESI)-MS/MS meth- od for determination of domperidone in human plasma.Methods:The analyte was treated by methanol precipitation to remove protein component from human plasma,then separated on a Phenomenex Gimini C_(18) column(2.00 mm× 50 mm,5μm).The mobile phase consisted of methanol-water(40:60,v/v,containing 0.3 % acetic acid),at a flow rate of 0.2 mL·min~(-1).A linear trap mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode.In multipole ion reaction monitoring(MRM)mode,the ion reac- tion combinations of m/z 426→m/z 175 and ra/z 379→m/z 264 were used to qualify domperidone and internal standard(ambroxol),respectively.Results:Chromatograms showed no endogenous interference peaks with the re- spective blank human plasma samples.Each analysis was completed with in 2 min.The calibration was linear in the concentration range of 0.3-100 ng·mL~(-1),and quantitative limit was 0.3 ng·mL~(-1).The intra-day and inter- day RSDs were less than 7.1% and 13.3%,respectively.The accuracy determined as relative error was less than 5.4%.Conclusion:The method is proved to be suitable for clinical investigation of pharmacokinetics of therapeutic dose of domperidone,which offers advantages of specificity,quickness,and sensitivity over the previously reported methods.

Key concepts: Chemistry, Chromatography, Domperidone, Protein precipitation, Electrospray ionization, Selected reaction monitoring, Detection limit, Analyte

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