Development of an isotope-dilution liquid chromatography/mass spectrometric method for the accurate determination of acetaminophen in tablets

Abstract

Acetaminophen (A-acetyl-p-aminophenol) is one of the most popular analgesic and antipyretic drugs. An isotope dilution mass spectrometric method based on LC/MS was developed as a candidate reference method for the accurate determination of acetaminophen in pharmaceutical product. After spiking an isotope labeled acetaminophen (acetyl-13C2, 15N- acetaminophen) as an internal standard, tablet extracts were analyzed by LC/MS in a selected reaction monitoring (SRM) mode to detect ions at m/z 152→110 and m/z 155→111 for acetaminophen and acetyl- 13C2, 15N-acetaminophen, respectively. The repeatability and reproducibility of the developed ID/LC-MS method were tested for the validation and assessment of metrological quality of the method.