Application of liquid chromatography-turbo ion spray tandem mass spectrometry for quantitative analysis of a potent motilin receptor agonist, EM574, and its metabolites in human plasma.
A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the simultaneous determination of a new potent motilin receptor agonist as erythromycin derivative, EM574 (erythromycin derivative), and its three metabolites, M-IV, M-V and M-VI, in human plasma was developed. The internal standards (I.S.s) used were deuterated EM574, M-IV and M-V. For the quantitation of M-VI, deuterated M-V was used. The analytes and I.S. were extracted from plasma samples with diethyl ether at neutral pH. A turbo ion spray interface was used as the ion source of LC-MS-MS, and the analysis was performed in the selected reaction monitoring mode. The lower quantitation limits for all the analytes were 0.05 ng/ml when 0.2 ml of plasma was used, and the standard curves were linear in the range 0.05 to 20 ng/ml. The method was precise; the intra- and inter-day precisions of the method were not more than 19.8% for all the analytes. The accuracy of the method was good with the deviations between added and calculated concentrations of each analyte being typically within +/- 11.2%.
Kondo
T
T
Drug Analysis and Pharmacokinetics Research Laboratories, Takeda Chemical Industries Ltd., Osaka, Japan. kondo_takahiro@takeda.co.jp
Dote
N
N
Hagimoto
T
T
Yoshimura
Y
Y
D002853:Chromatography, Liquid / Q000379:methods*; D003903:Deuterium; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists*; D018013:Receptors, Neuropeptide / Q000819:agonists*; D012680:Sensitivity and Specificity
D005765:Gastrointestinal Agents; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; C090116:Idremcinal; D004917:Erythromycin; D003903:Deuterium