Development and validation of a sensitive LC-MS/MS method for the estimation of scopolamine in human serum

Suresh Kumar Swaminathan, James Fisher, Nicole K. Brogden, Karunya K Kandimalla

Research output: Contribution to journalArticle

Abstract

Scopolamine is an anticholinergic alkaloid that is widely used in the form of a transdermal system to manage nausea associated with motion sickness. Currently available methods to quantify scopolamine require large sample volumes and involve cumbersome sample preparation. In this work, a simple method for the rapid separation and sensitive quantification of scopolamine in human serum was developed. Scopolamine was extracted from 0.5 mL of human serum using solid-phase extraction. The extracted samples were injected onto Zorbax XDB-C18 column (4.6 × 50 mm, 1.8 μm, and 600 bar) on an Agilent 1200 series HPLC. The chromatographic separation involved gradient elution with water and acetonitrile containing 0.1% v/v formic acid as a mobile phase. The samples were quantified in positive ion mode using a TSQ Quantum triple quadrupole mass spectrometer. The assay was validated and found to be linear over a concentration range of 5–5000 pg/mL. The total assay precision and accuracy was 6.3% and 96%, respectively. The lower limit of quantification (LLOQ) of the assay was 5 pg/mL. The assay was used in a human pharmacokinetic study to measure the concentration of scopolamine in serum after an administering scopolamine as transdermal delivery system or as an intravenous bolus dose.

LanguageEnglish (US)
Pages41-46
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume164
DOIs
StatePublished - Feb 5 2019

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Scopolamine Hydrobromide
Assays
Serum
formic acid
Motion Sickness
Pharmacokinetics
Solid Phase Extraction
Cholinergic Antagonists
Mass spectrometers
Alkaloids
Nausea
Positive ions
High Pressure Liquid Chromatography
Ions
Water

Keywords

  • Human serum
  • Liquid chromatography
  • Mass spectrometry
  • Scopolamine
  • Solid-phase extraction

Cite this

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title = "Development and validation of a sensitive LC-MS/MS method for the estimation of scopolamine in human serum",
abstract = "Scopolamine is an anticholinergic alkaloid that is widely used in the form of a transdermal system to manage nausea associated with motion sickness. Currently available methods to quantify scopolamine require large sample volumes and involve cumbersome sample preparation. In this work, a simple method for the rapid separation and sensitive quantification of scopolamine in human serum was developed. Scopolamine was extracted from 0.5 mL of human serum using solid-phase extraction. The extracted samples were injected onto Zorbax XDB-C18 column (4.6 × 50 mm, 1.8 μm, and 600 bar) on an Agilent 1200 series HPLC. The chromatographic separation involved gradient elution with water and acetonitrile containing 0.1{\%} v/v formic acid as a mobile phase. The samples were quantified in positive ion mode using a TSQ Quantum triple quadrupole mass spectrometer. The assay was validated and found to be linear over a concentration range of 5–5000 pg/mL. The total assay precision and accuracy was 6.3{\%} and 96{\%}, respectively. The lower limit of quantification (LLOQ) of the assay was 5 pg/mL. The assay was used in a human pharmacokinetic study to measure the concentration of scopolamine in serum after an administering scopolamine as transdermal delivery system or as an intravenous bolus dose.",
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