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Quantification of urapidil, α ‐1‐adrenoreceptor antagonist, in plasma by LC‐MS/MS: validation and application to pharmacokinetic studies
Author(s) -
Nirogi Ramakrishna,
Kandikere Vishwottam,
Komarneni Prashanth,
Aleti Raghupathi,
Boggavarapu Rajesh,
Madala Pavankumar
Publication year - 2011
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1604
Subject(s) - urapidil , chemistry , chromatography , pharmacokinetics , cmax , analyte , selected reaction monitoring , liquid chromatography–mass spectrometry , electrospray ionization , tandem mass spectrometry , extraction (chemistry) , mass spectrometry , pharmacology , medicine , heart rate , blood pressure , radiology
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. Copyright © 2011 John Wiley & Sons, Ltd.