, and reagentgrade ammonium acetate were purchased from EM Sciences (Gibbstown, NJ, USA). Bovine plasma was acquired from Sigma Chemical Company.

Standard and Sample Preparation: Primary stock solutions of cabergoline and the internal standard pergolide (Figure 1) were each prepared at a concentration of 1 mg/mL in methanol and stored at 25 C. A plasma solution was prepared by precipitating bovine plasma with a 2 volume of acetonitrile. A 1 g/mL cabergoline plasma standard was prepared by spiking the precipitated bovine plasma with the cabergoline stock solution. Working plasma standards were prepared by sequentially diluting the 1 g/mL cabergoline plasma standard with the precipitated bovine plasma solution to yield final concentrations ranging from 10 pg/mL to 1 g/mL. Prior to analysis, each standard level was spiked with the pergolide stock solution to produce the fixed internal standard concentration of 200 ng/mL of pergolide. The plasma standards were then ready for direct injection into the HPLCno further sample clean up was necessary.


Figure 1. Structures of cabergoline and pergolide.



Figure 2. LC/ESI/SRM chromatogram of 50 fg on column of cabergoline (m/z 452 381) and 1 ng on column of pergolide internal standard (m/z 315208) in plasma under unit resolution conditions.



Figure 3. LC/ESI/SRM chromatograms of drug-free plasma under unit resolution conditions.

Sample Analysis: HPLC analysis was performed on the Thermo Finnigan Surveyor LC System. The chromatographic separation was performed using isocratic conditions on an XTerra MS C18, 5 m, 2.1 150 mm column (Waters Corporation, Milford, MA, USA) with a mobile phase of acetonitrile/ ammonium acetate (60:40, v/v). The LC flow rate was 0
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