TY - JOUR
T1 - Development and validation of a sensitive LC-MS/MS method for the estimation of scopolamine in human serum
AU - Swaminathan, Suresh Kumar
AU - Fisher, James
AU - Brogden, Nicole K.
AU - Kandimalla, Karunya K.
N1 - Publisher Copyright:
© 2018
PY - 2019/2/5
Y1 - 2019/2/5
N2 - 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.
AB - 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.
KW - Human serum
KW - Liquid chromatography
KW - Mass spectrometry
KW - Scopolamine
KW - Solid-phase extraction
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UR - http://www.scopus.com/inward/citedby.url?scp=85055798544&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2018.09.051
DO - 10.1016/j.jpba.2018.09.051
M3 - Article
C2 - 30396054
AN - SCOPUS:85055798544
SN - 0731-7085
VL - 164
SP - 41
EP - 46
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -