title: Liquid chromatography-mass spectrometric method for determination of the non-imidazole H3-receptor antagonist UPR1056 in rat plasma.
abstract: The non-imidazole H3 receptor antagonist UPR1056 was dosed in plasma samples from rats individually administered with a single i.p. dose of 1.25 mg/kg by means of a newly validated HPLC-MS method. UPR1056 was extracted from rat plasma by protein precipitation with acetonitrile and was separated by linear gradient elution, employing water and methanol both additioned with 0.05% trifluoroacetic acid as mobile phases. UPR1056 was detected in MS using an electrospray ion source operating in positive ion mode. Acquisition was performed in single ion monitoring mode at m/z=349.3. The method was validated over the concentration range of 17.43-1743 ng/mL (50-5000 pmol/mL). Within- and between-run precision for the low, mid and high quality controls (QC) levels were 6.75% or less and accuracy ranged from 95.8 to 107.6%. The lower limit of quantification was 17.43 ng/mL. The analysis of the time course of UPR1056 concentrations over the 24-h period revealed a C(max) of 1147 ng/mL after 2 h from peripheral administration of the non-imidazole H(3)-receptor antagonist, with a prolonged elimination half-life of over 9 h.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, Parma, Italy. federica.vacondio@unipr.it
authors.forename: Federica
authors.initials: F
authors.lastname: Vacondio
authors.forename: Claudia
authors.initials: C
authors.lastname: Silva
authors.forename: Giovanni
authors.initials: G
authors.lastname: Morini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bordi
authors.forename: Lisa
authors.initials: L
authors.lastname: Flammini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D006633:Histamine Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D006633:Histamine Antagonists; D018100:Receptors, Histamine H3