Page 4 - Clinical-Medical Solution for Clinical Chemistry

LAAN-A-LM-E094

Application Liquid Chromatography Mass Spectrometry

News High-Throughput Optimization of Therapeutic Drug

Monitoring Using Fully Automated Sample Preparation
No.C123 LC/MS/MS System (CLAM-2000 + LCMS-8040)

Therapeutic drug monitoring (TDM) is a series of This article introduces the results of TDM using a fully
processes where the blood concentration of drugs in a automated sample preparation LC/MS/MS system
patient is measured to determine the optimal dose and comprised of the CLAM-2000 fully automated LCMS
method of administration for an individual based on sample preparation unit and the LCMS-8040 high
pharmacokinetic and pharmacodynamic analysis. TDM performance liquid chromatograph-mass spectrometer.
is used during drug treatment with drugs that pose This system resolves the above-mentioned problems
administration management difficulties, such as drugs associated with TDM, and achieves TDM research results
with a narrow therapeutic range or with an effective on a fast and high-precision analytical workflow.
range and toxic range that are close to each other. High
performance liquid chromatography (HPLC) has been
the main analytical method used with TDM, but recently
liquid chromatography-mass spectrometry (LC/MS/MS)
is being used to improve analytical accuracy and
precision based on its superior selectivity.
LC/MS/MS normally requires sample preparation steps
such as deproteinization and dilution to analyze a blood
serum or blood plasma sample. These steps introduce
the risk of error or variability occurring based on
operator skill. The volume of work performed by an
operator also increases in accordance with the number
of samples. Therefore, the sample preparation process
can become the bottleneck of an analytical workflow
when analyzing a large number of samples. Fully Automated Sample Preparation LC/MS/MS System

n High-Throughput Analytical Workflow for
Antiepileptic Drug Analysis
We introduce an example simultaneous analysis of requires placing of the blood collection tube in the
seven antiepileptic drugs and drug active metabolites in system, as the system performs all these preparation
blood serum using a fully automated sample steps automatically, followed by LC/MS/MS analysis
preparation LC/MS/MS system. (Fig. 1).
Preparation of blood serum samples for analysis Preparation of the next sample can also be performed
normally requires deproteinization by the addition of in parallel with LC/MS/MS analysis, which can greatly
organic solvent, and then centrifugal separation of solid reduce the time required for each sample analysis. In
components followed by supernatant recovery. The fully our example, a per-sample cycle time including analysis
automated sample preparation LC/MS/MS system only of 9 minutes is achieved.

Preparation of the Sample injection Sample injection Sample injection
blood collection tube 9 min 9 min
Setting of blood collection
tube and reagents in system MS analysis MS analysis MS analysis
7 min 7 min 7 min
Serum
Deproteinization step Deproteinization step Deproteinization step
8 min 8 min 8 min

Deproteinization using the CLAM-2000
Sample Reagent Stirring Filtration
injection injection • Rotation • PTFE membrane
• Freeze-dried • Methanol speed • Pore size:
blood serum • 270 µL 1800 rpm 0.45 µm
• 30 µL • Time: • Pressure:
-50 to -60 kPa
150 sec
• Time: 150 sec
Fig. 1 Workflow for Simultaneous Analysis of Antiepileptic Drugs in Blood Serum Using Fully Automated Sample Preparation LC/MS/MS System