Development and validation of a sensitive solid-phase-extraction (SPE) method using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) for determination of risedronate concentrations in human plasma

Ghassabian, Sussan, Wright, Linda A., deJager, Andrew D. and Smith, Maree T. (2012) Development and validation of a sensitive solid-phase-extraction (SPE) method using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) for determination of risedronate concentrations in human plasma. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 881-82 34-41. doi:10.1016/j.jchromb.2011.11.031


Author Ghassabian, Sussan
Wright, Linda A.
deJager, Andrew D.
Smith, Maree T.
Title Development and validation of a sensitive solid-phase-extraction (SPE) method using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) for determination of risedronate concentrations in human plasma
Journal name Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences   Check publisher's open access policy
ISSN 1570-0232
1873-376X
Publication date 2012-01-15
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.jchromb.2011.11.031
Volume 881-82
Start page 34
End page 41
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2012
Language eng
Formatted abstract
Risedronate is a commonly prescribed bisphosphonate for the treatment of bone disorders. Due to its high polarity and low oral bioavailability, low concentrations of risedronate are expected in human plasma and therefore a sensitive assay is required to serve in pharmacokinetic studies. Here, we describe the development and validation of an LC–MS/MS assay for the measurement of risedronate concentrations in human plasma. Risedronate and the internal standard, risedronate-d4, were derivatized on an anion exchange solid-phase extraction cartridge. Trimethylsilyl-diazomethane which is a thermally stable and relatively non-toxic derivatization agent was used to methylate the risedronate phosphonic acid groups and decrease analyte polarity. Following extraction, the analytes were separated on a Phenomenex Gemini C18 column (150 mm × 2.0 mm, 5 μm), using a gradient of ammonium acetate 10 mM and acetonitrile with a flow rate of 300 μL/min. The assay calibration range was 0.2–25 ng/mL. The calibration curve of risedronate standards spiked in six individual plasma samples was linear (r2 = 0.9998). Accuracy (percent deviation from nominal) and precision (percent coefficient of variation) at concentrations 0.5, 5 and 20 ng/mL, and at the lower limit of quantification (LLOQ) of 0.2 ng/mL were excellent at <6%. Mean recovery was 54% for risedronate and 51% for the internal standard. Risedronate was stable in human plasma samples for at least 5 h at room temperature, 101 days frozen at −80 °C, 72 h in an autosampler at 10 °C, and for three freeze/thaw cycles. The validated assay method successfully quantified the concentrations of risedronate in plasma samples from informed consenting healthy volunteers administered a single 35 mg risedronate tablet.
Keyword Risedronate
Bisphosphonate
Liquid chromatography/tandem mass spectrometry (LC-MS/MS)
Trimethylsilyldiazomethane
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 28 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Centre for Integrated Preclinical Drug Development Publications
 
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