An LC-MS/MS assay for the quantitative determination of 2-pyridyl acetic acid, a major metabolite and key surrogate for betahistine, using low-volume human K 2 EDTA plasma

Betahistine is widely used for the treatment of vertigo. Owing to first-pass metabolism, 2-pyridyl acetic acid (2PAA, major metabolite of betahistine) was considered as surrogate for quantitation. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of 2PAA using tur...

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Bibliographic Details
Published in:Biomedical chromatography 2017-02, Vol.31 (2)
Main Authors: Soni, Krunal, Bhatt, Chandrakant, Singh, Kanchan, Bhuvaneshwari, P C, Jha, Anil, Patel, Palak, Patel, Harilal, Srinivas, Nuggehally R
Format: Article
Language:English
Subjects:
Acetates - blood
Acetates - metabolism
Betahistine - blood
Betahistine - metabolism
Chromatography, High Pressure Liquid - methods
Edetic Acid - blood
Humans
Limit of Detection
Pyridines - blood
Pyridines - metabolism
Sample Size
Solid Phase Extraction - methods
Tandem Mass Spectrometry - methods
Vasodilator Agents - blood
Vasodilator Agents - metabolism
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Summary:Betahistine is widely used for the treatment of vertigo. Owing to first-pass metabolism, 2-pyridyl acetic acid (2PAA, major metabolite of betahistine) was considered as surrogate for quantitation. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of 2PAA using turbo-ion spray in a positive ion mode. A solid-phase extraction was employed for the extraction of 2PAA and 2PAA d (IS) from human plasma. Chromatographic separation of analytes was achieved using an ACE CN, 5 μm (50 × 4.6 mm) column with a gradient mobile phase comprising acetonitrile-methanol (90:10% v/v) and 0.7% v/v formic acid in 0.5 mm ammonium trifluoroacetate in purified water (100% v/v). The retention times of 1.15 and 1.17 min for 2PAA and internal standard, respectively, were achieved. Quantitation of 2PAA and internal standard was achieved by monitoring multiple reaction monitoring transition pairs (m/z 138.1 to m/z 92.0 and m/z 142.1 to m/z 96.1, respectively). The developed method was validated for various parameters. The calibration curves of 2PAA showed linearity from 5.0 to 1500 ng/mL, with a lower limit of quantitation of 5.0 ng/mL. The bias and precision for inter- and intra-batch assays were
ISSN:0269-3879
1099-0801
DOI:10.1002/bmc.3790