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Validation of a sensitive and specific LC–MS/MS method and application to evaluate the systemic exposure and bioavailability of glycopyrrolate via different drug delivery approaches/devices
Author(s) -
Shi Lei,
Ngounou Wetie Armand Gatien,
Wang Weimin,
Chen YuLuan
Publication year - 2020
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.4899
Subject(s) - chemistry , chromatography , formic acid , glycopyrrolate , ammonium acetate , bioavailability , bioanalysis , absorption (acoustics) , solid phase extraction , elution , detection limit , melamine , high performance liquid chromatography , pharmacology , atropine , materials science , medicine , organic chemistry , anesthesia , composite material
A specific and sensitive LC–MS/MS method using d 3 ‐glycopyrrolate as the internal standard (IS) was developed for the quantitative determination of glycopyrrolate (GLY) in human plasma over a concentration range of 4.00–2000 pg/ml. The GLY and IS were extracted using a solid‐phase extraction cartridge, then eluted with 0.5% formic acid in 70:30 acetonitrile–water. The eluate was directly injected into an Agilent Pursuit 5PFP column for analysis using an isocratic mobile phase of 50:50 A:B at a flow‐rate of 0.500 ml/min (A, 10 m m ammonium acetate in 1% formic acid; B, methanol). The MS detection was in positive mode by monitoring m/z 318.3 → 116.1 (GLY) and 321.3 → 119.1 (IS). The method validation showed the linearity of r 2 ≥ 0.9960, intra‐/inter‐run precisions of ≤11.1% coefficient of variation and accuracies ranging from −2.5 to 12.8% relative error for all levels of quality control samples. This method was successfully employed to support a clinical study to compare absorption and bioavailability of GLY administered by a Magnair ® eFlow nebulizer to a Seebri ® Breezhaler ® with/without a charcoal blockade of gastric absorption. By comparison with intravenous administration, respective bioavailabilities of ~15% for GLY/Magnair and ~22% for the Seebri Breezhaler were found. The bioanalytical reliability was also demonstrated by satisfactory incurred sample reanalysis performance.