title: Quantification of urapidil, α-1-adrenoreceptor antagonist, in plasma by LC-MS/MS: validation and application to pharmacokinetic studies.
abstract: A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of urapidil in plasma. Following liquid-liquid extraction, the analyte was separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 388 to 205 for urapidil and m/z 452 to 344 for the internal standard. The assay exhibited a linear dynamic range of 0.1-500 ng/mL for urapidil in plasma. Acceptable precision (<7%) and accuracy (100 ± 8%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify urapidil concentrations in a preclinical pharmacokinetic study after a single oral administration of urapidil at 3 mg/kg to rats. Following oral administration the maximum mean concentration in plasma (C(max); 616 ± 73 ng/mL) was achieved at 0.5 h (T(max)) and area under curve (AUC(0-24)) was 1841 ± 308 ng h/mL. The half-life (t(1/2)) and clearance (Cl) were 2.47 ± 0.4 h and 1660 ± 276 mL/h/kg, respectively. Moreover, it is plausible that the assay method in rat plasma would facilitate the adaptability of urapidil quantification in human plasma for clinical trials.
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: Pavankumar
authors.initials: P
authors.lastname: Madala
mesh_terms: D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D016018:Least-Squares Analysis; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; C015568:urapidil