Gas chromatography/negative-ion chemical ionisation mass spectrometry for the quantitative analysis of morphine in human plasma using pentafluorobenzyl carbonate derivatives

Rapid Communications in Mass Spectrometry : RCM
H J LeisG Fauler

Abstract

A sensitive and specific method for the quantitative determination of morphine in human plasma is presented. Morphine was extracted from plasma by solid phase extraction on C18 and converted to its pentafluorobenzyl carbonate trimethylsilyl derivative. The derivatives were analysed without further purification. Using gas chromatography/negative ion chemical ionisation mass spectrometry, a useful diagnostic fragment ion at m/z 356 is obtained at high relative abundance. Deuterated morphine was used as internal standard. Calibration graphs were linear within the range 1.25 to 320 nmol/L. Intra-day precision was 3.82% (15 nmol/L), 2.85% (75 nmol/L) and 4.13% (225 nmol/L), inter-day variability was found to be 1.77% (15 nmol/L), 4.95% (75 nmol/L) and 9.88% (225 nmol/L). Inter-day accuracy showed deviations of 2.18% (15 nmol/L), -0.72% (75 nmol/L) and -0.13% (225 nmol/L). The method is rugged and robust and has been applied to the batch analysis of morphine during pharmacokinetic profiling of the drug.

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Citations

May 1, 2007·Analytical and Bioanalytical Chemistry·Thomas Kraemer, Liane D Paul
Jul 12, 2002·Journal of Mass Spectrometry : JMS
Jun 28, 2003·Natural Product Reports·Kenneth W Bentley
Aug 30, 2003·Analytical Chemistry·T A BrettellR Saferstein

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