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Quantitation of Cabergoline at Extremely Low Plasma Concentrations with ,,, a Triple Quadrupole Mass Spectrometer

phy coupled with tandem mass spectrometry (LC/MS/MS). Techniques utilizing HPLC alone proved to have insufficient detection limits.[3,4] RIA also does not have an adequate lower limit of quantitation (LLOQ) suitable for monitoring cabergoline when administered at low doses.[1,5] And while recent LC/MS/MS methods have shown improvement in sensitivity through the use of selected reaction monitoring (SRM), they still require large sample volumes and time-consuming sample preparation.[6,7] Consequently, these methods either lack the sensitivity, dynamic range, or practicality required for routine, high-throughput pharmacokinetic applications. To assess the feasibility of using the TSQ Quantum to address these application requirements, cabergoline was analyzed in the LC/ESI/SRM, unit-resolution mode. Significant improvement in sensitivity was demonstrated on the TSQ Quantum compared to the previous generation triple quadrupole mass spectrometer from Thermo Finnigan, the TSQ 7000.[811] Using the TSQ Quantum, low femtogram-levels of cabergoline were resolved from the complex plasma matrix. Excellent precision and accuracy were maintained over five orders of magnitude, demonstrating a linear dynamic range suitable for real-world, pharmacokinetic applications.[8,9,12]

Goals

1) Analyze low-level plasma concentrations of cabergoline in a complex matrix.

2) Demonstrate a dynamic linear response of method more suitable for pharmacokinetic applications.

3) Compare the method performance of the TSQ Quantum to that of an earlier-generation mass spectrometer.

Experimental Conditions

Chemicals and Reagents: Cabergoline (purity >99%) was chemically synthesized. Pergolide mesylate (purity >98%) was supplied by Sigma Chemical Company (St. Louis, MO, USA). HPLCgrade acetonitrile and methanol
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