Quantification of the bombesin/gastrin releasing peptide antagonist RC-3095 by liquid chromatography–tandem mass spectrometry

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Bombesin (BN) and its mammalian equivalent, gastrin-releasing peptide (GRP), stimulate cell proliferation and are involved in the pathogenesis of several types of human cancer. BN/GRP and their receptors were shown to be critical for the growth of various human malignancies, such as small-cell lung, prostate, ovary, stomach and breast cancers in the human tumor xenograft model. In the present study, a fast, sensitive, robust method was developed for the determination and quantification of a BN/GRP receptor antagonist RC-3095 (D-Tpi-Gln-Trp-Ala-Val-Gly-His-Leuψ(CH2NH)Leu-NH2), in human plasma by liquid chromatography coupled with tandem mass spectrometry. RC-3095 was extracted from 0.2 ml human plasma by protein precipitation using cold acetonitrile (0.4 ml). The method has a chromatographic run of 10 min using a C 8 analytical column (150 mm × 4.6 mm i.d.) and the linear calibration curve over the range was linear from 20 to 10000 ng ml −1 ( r 2 > 0.994). The between-run precision, based on the relative standard deviation replicate quality controls, was 5.7% (60 ng ml −1), 7.1% (600 ng ml −1) and 6.8% (8000 ng ml −1). The between-run accuracy was ±0.0, 2.1 and 3.1% for the above-mentioned concentrations, respectively. The developed procedure allows the quantitative determination of peptide RC-3095 for pharmacokinetics studies in human plasma.