Page 8 - Clinical-Medical Solution for Clinical Chemistry
P. 8

LAAN-A-LM-E123







            Application                  Liquid Chromatograph Mass Spectrometry

            News                         Simultaneous Analysis of Antiarrhythmic Drugs in

                                         Human Blood Plasma Using the Fully Automated
            No. C153                     Sample Preparation LC/MS/MS System



            During drug treatment  with drugs  that pose       „  Analysis of Antiarrhythmic Drugs in Blood
            administration management difficulties, such as drugs   Plasma with Fully Automated Pretreatment
            with a narrow therapeutic range or drugs with a fine   Pretreatment of blood plasma samples for analysis
            line between toxicity and  effectiveness, the blood   normally  requires  a  process  that  involves
            concentration of drugs in patients is  measured to   deproteinization by adding an organic solvent,
            determine the optimal dose and method of           followed  by   centrifugal  separation  of  solid
            administration  for   individuals  based   on      components and supernatant isolation. With the fully
            pharmacokinetic and pharmacodynamic analysis.      automated sample preparation LC/MS/MS system,
            Application  News   No.  C123   introduced  an     these preparatory steps are done automatically just by
            investigation  into optimizing the analysis workflow   setting a blood collection tube after blood plasma
            including pretreatment by using the fully automated   separation, and LC/MS/MS analysis is continuously
            sample preparation LC/MS/MS system that comprises   performed (Fig. 1). Pretreatment of the next sample can
            the CLAM-2000 fully automated LCMS sample          also be performed in parallel with LC/MS/MS analysis,
            preparation  unit and a high performance liquid    which can greatly reduce the time required for each
            chromatograph mass spectrometer.
                                                               sample analysis.
            This article introduces a study which achieves a fast and   In this analysis example, a per-sample cycle time of 7
            simultaneous analysis workflow of six antiarrhythmic
            drugs with the fully automated sample  preparation   minutes  was  achieved  from  blood   plasma
                                                               pretreatment to the simultaneous analysis of six
            LC/MS/MS system.
                                                               antiarrhythmic drugs and metabolites using LC/MS/MS
                                        T. Tsukamoto, D. Kawakami
                                                               (Table 1 and Fig. 2).





















                                             Pretreatment Workflow of Blood Plasma Samples

                  Table 1  Antiarrhythmic Drugs and Metabolites   (x10,000,000)
                                                                     1: Amiodarone
                                                 MRM            1.25  2: Desethylamiodarone
                                 Molecular
                 Compound                      Transition            3: Bepridil
                                  Formula                            4: Flecainide              1
                                                 m/z            1.00  5: Pilsicainide
                                                                     6: Cibenzoline            2
                 Amiodarone      C25H29I2NO3   646.0 > 58.1          7: Mexiletine           3
                                                                0.75
              Desethylamiodarone   *  C23H25I2NO3   618.0 > 72.1
                   Bepridil      C24H34N2O     367.1 > 84.1     0.50               5    4
                  Flecainide     C17H20F6N2O3   415.0 > 301.0
                                                                                       6
                 Pilsicainide    C17H24N2O    272.9 > 110.1     0.25
                                                                                     7
                 Cibenzoline      C18H18N2    262.9 > 115.0
                                                                0.00
                  Mexiletine      C11H17NO     180.1 > 58.0
                                                                  0.0    0.5    1.0    1.5    2.0    2.5   min
                                                                        Mass Chromatograms of Human Blood Plasma
                                                                             with Standard Additives
   3   4   5   6   7   8   9   10   11   12   13