title: Quantification of the bombesin/gastrin releasing peptide antagonist RC-3095 by liquid chromatography-tandem mass spectrometry.
abstract: 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-Leupsi(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 x 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.
authors.affiliation: Galeno Research Unit, Latino Coelho St., 1301, Parque Taquaral, 13087-010 Campinas, SP, Brazil.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pereira
authors.forename: Luciane
authors.initials: L
authors.lastname: DiLeone
authors.forename: Fabiano H
authors.initials: FH
authors.lastname: Souza
authors.forename: Sergio
authors.initials: S
authors.lastname: Lilla
authors.forename: Marc
authors.initials: M
authors.lastname: Richter
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
mesh_terms: D001839:Bombesin / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D010446:Peptide Fragments / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results
chemical_list: D010446:Peptide Fragments; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D001839:Bombesin