Analysis of Paracetamol Using Solid-Phase Extraction, Deuterated Internal Standards, and Gas Chromatography-Mass Spectrometry

Abstract

A rapid method for determining paracetamol (acetaminophen) in whole blood and liver tissue samples is described. Blank plus single-point calibration gives reliable quantitation at therapeutic and higher concentrations. Whole blood and liver tissue samples containing a deuterated internal standard were extracted using Bond Elut Certify columns. Butyl derivatives were formed using n-iodobutane and tetramethyl ammonium hydroxide under mild conditions and were extracted into ethyl acetate as a cleanup step. Recovery was better than 90%, and sample preparation time was less than 2 h. Gas chromatograph run time was less than 20 min. SIM of two ion pairs formed by electron impact ionization resulted in intraday coefficients of variation (CV) less than 3.03% (7.48% in liver) and interday CVs less than 8.93% (for midtherapeutic concentrations in whole blood). Linearity was observed from subtherapeutic to high, fatal levels. This method has been applied to forensic cases and has significantly reduced analytical time while improving casework quality. Results of a case study involving paracetamol are given.

Evaluation of paracetamol distribution and stability in case of acute intoxication in rats

“…18 The results of our study related to serum samples correlate with the study of Speed and his friends although they are not identical in the purpose of the studies. In our study, it was observed that the amount of paracetamol in liver stored at À20 C decreased with each passing day.…”

Rapid and accurate amperometric determination of acetaminophen in pharmaceutical preparations and spiked human blood serum samples at cadmium pentacyanonitrosylferrate modified glassy carbon electrode

“…Numerous methods have been used for the determination of paracetamol in pharmaceutical formulations and biological fluids including titrimetry [5,6], UV-Vis spectrophotometry [7][8][9][10], spectrofluorimetry [11], near infrared transmittance spectroscopy [12], electrochemical methods [13,14], and chromatography [10,[15][16][17][18][19]. Recently, several flow injection (FI) methods for the determination of paracetamol have been proposed using an UV-Vis spectrophotometer [20][21][22], fluorimeter [23], multioptosensor [24], or Fourier transform infrared spectrophotometer [25] as a detector.…”

Simultaneous Determination of Paracetamol and Tramadol in Pharmaceutical Tablets by Derivative UV-Vis Absorption Spectrophotometry

“…Analysis, with codeine phosphate, using a RP-HPLC system with manual injector has also been reported [20]. Solid-phase extraction, using deuterated internal standards, and gas chromatography-mass spectrometry has also been used [21].…”