title: Quantification of methyllycaconitine, selective α7 nicotinic receptor antagonist, in rodent plasma and brain tissue by liquid chromatography tandem mass spectrometry--application to neuropharmacokinetics of methyllycaconitine in rats.
abstract: A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of methyllycaconitine (MLA) in rat plasma and brain tissue. Following acetonitrile protein precipitation, the analyte was separated using a gradient mobile phase on a reversed-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 683-216 for MLA and m/z 260-116 for the internal standard. The assay exhibited a linear dynamic range of 0.5-250 ng/mL for MLA in rat plasma and brain tissue. The lower limit of quantification was 0.5 ng/mL. Acceptable precision (<12%) and accuracy (100 ± 6%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify MLA concentrations in a rodent pharmacokinetic and brain penetration study.
authors.affiliation: Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad, 500034, India. ramakrishna_nirogi@yahoo.co.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.forename: Vishwottam
authors.initials: V
authors.lastname: Kandikere
authors.forename: Prashanth
authors.initials: P
authors.lastname: Komarneni
authors.forename: Raghupathi
authors.initials: R
authors.lastname: Aleti
authors.forename: Rajesh
authors.initials: R
authors.lastname: Boggavarapu
authors.forename: Gopinadh
authors.initials: G
authors.lastname: Bhyrapuneni
authors.forename: Nageswararao
authors.initials: N
authors.lastname: Muddana
authors.forename: K
authors.initials: K
authors.lastname: Mukkanti
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D016014:Linear Models; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C054634:methyllycaconitine; D000157:Aconitine