title: Quantification of cinacalcet by LC-MS/MS using liquid-liquid extraction from 50 μL of plasma.
abstract: A simple and economical high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of cinacalcet in plasma. Following liquid-liquid extraction, the analyte was separated using an isocratic 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 358-155 for cinacalcet and m/z 310-148 for the internal standard. The assay exhibited a linear dynamic range of 0.1-200 ng/mL for cinacalcet in plasma. Acceptable precision (<10%) and accuracy (100±5%) were obtained for concentrations over the standard curve range. A run time of 3.5 min for each sample made it possible to analyze more than 250 samples per day. The method was successfully applied to quantify cinacalcet concentrations in a preclinical pharmacokinetic study after a single oral administration of cinacalcet at 10 mg/kg to rats. Following oral administration the maximum mean concentration in plasma (C(max); 160±56 ng/mL) was achieved at 1.0 h (T(max)), area under the curve (AUC) and half-life (t(½)) were 949±257 ng h/mL and 3.58±0.4 h, respectively.
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: Nagasuryaprakash
authors.initials: N
authors.lastname: Padala
authors.forename: Ilayaraja
authors.initials: I
authors.lastname: Kalaikadiban
mesh_terms: D000284:Administration, Oral; D000818:Animals; D057966:Calcimimetic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D005591:Chemical Fractionation; D002853:Chromatography, Liquid / Q000592:standards; D056148:Chromatography, Reverse-Phase; D000069449:Cinacalcet; D004986:Ether / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D008954:Models, Biological; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D057966:Calcimimetic Agents; D009281:Naphthalenes; D012997:Solvents; D004986:Ether; D008752:Methylene Chloride; D000069449:Cinacalcet