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 |
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Authors: | Ramakrishna Nirogi Vishwottam Kandikere Prashanth Komarneni Raghupathi Aleti Rajesh Boggavarapu Gopinadh Bhyrapuneni Nageswararao Muddana K. Mukkanti |
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Affiliation: | 1. Discovery Research, Suven Life Sciences Ltd, , Banjara Hills, Hyderabad, 500034 India;2. Institute of Science and Technology, JNT University, , Kukatpally, Hyderabad, 500072 India |
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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. Copyright © 2011 John Wiley & Sons, Ltd. |
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Keywords: | methyllycaconitine liquid chromatography‐tandem mass spectrometry plasma brain tissue pharmacokinetic study |
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