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Femtogram Sensitivity of the Antipsychotic Drugs Raclopride and Ritanserin Using a Varian 1200L LC/MS/MS

J. Beck and C. Schmidt
Varian, Inc.

Introduction

Ritanserin (Tisterton) is a serotonin-2 antagonist drug shown to be effective in the treatment of anxiety and depression1 while Raclopride acts as a dopamine D2 receptor antagonist.2 These two compounds were used to demonstrate low-level sensitivity of the Varian 1200L LC/MS/MS in selected reaction monitoring mode (SRM). Studies have shown LC/MS to be a useful tool in the quantitation of low levels of Raclopride.3

Instrumentation

Varian 1200L LC/MS/MS equipped with ESI source

Materials and Reagents

Ritanserin ordered from Sigma-Aldrich Corp.,Catalog Number R-103

S-(-)-Raclopride ordered from Sigma-Aldrich Corp.,Catalog Number R-121

All other chemicals are reagent grade or HPLC grade

Sample Preparation

Milligram quantities were prepared and dissolved in a 50:50 mixture of acetonitrile/water with 0.1% formic acid. Serial dilutions were made from each stock solution prior to flow injection analysis (FIA). Samples were injected into a mobile phase of 50:50 acetonitrile/0.1% formic acid which was pumped directly into the mass spectrometer at 0.2 mL/min. A 5 μL loop was used for the injections and the injections were repeated five times for each concentration level.

Results and Discussion

Raclopride Five replicates at five different concentration levels were run. FIA injections of Raclopride at its lowest detectable limit, 100 pg/mL (500 fg on-column), is shown in Figure 1. At the lowest level, the S/N ratio is approximately 10:1 for the raw data. Also, a plot at a higher concentration of 10 ng/mL is included for comparison (Figure 2). The calibration cur
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