A reliable LC‐MS/MS method for the quantification of N‐acetyl‐p‐benzoquinoneimine, acetaminophen glutathione and acetaminophen glucuronide in mouse plasma, liver and kidney: Method validation and application to a pharmacokinetic study

Abstract

A rapid, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated to simultaneously quantify N-acetyl-p-benzoquinoneimine (NAPQI), acetaminophen-glutathione (acetaminophen-glut) and acetaminophen-glucuronide (acetaminophen-gluc) in mouse plasma, liver and kidney homogenates. Analytes were eluted by a binary gradient mobile phase composed of water (phase A) and methanol containing 0.1% formic acid (phase B) at a flow rate of 0.3 mL/min, which was performed on a CAPCELL PAK C MG II column. It took 3.2 min to detect three analytes in a single run. Quantification was carried out in positive mode combined with multiple reaction monitoring. The validation of the LC-MS/MS method consisted of specificity, linearity, precision, accuracy, protein precipitation recovery, matrix effect, dilution integrity and stability. The plasma and tissue homogenate calibration curves were linear over concentration ranges of 0.050-5.00, 0.050-5.00 and 0.100-40.0 μg/mL, with a lower limit of quantification of 0.050, 0.050, and 0.100 μg/mL for NAPQI, acetaminophen-glut and acetaminophen-gluc, respectively. The intra- and inter-run precision values were within 12.47% for NAPQI, 12.11% for acetaminophen-glut and 11.86% for acetaminophen-gluc at their lower limit of quantitation levels. The samples were stable under all tested conditions. This method was successfully applied to study the pharmacokinetics of NAPQI, acetaminophen-glut and acetaminophen-gluc in ICR mice following oral administration of 200 mg/kg of acetaminophen suspension.

Efflux Transporters in Rat Placenta and Developing Brain: Transcriptomic and Functional Response to Paracetamol

“…The plasma concentrations in our study were similar. Previous studies in rats and humans have found that the major metabolites of paracetamol are paracetamol-sulphate [27] [28] and paracetamol-glucuronide [23] [25] [29]. Thirty minutes after administration maternal plasma paracetamol-sulphate was twice the concentration of paracetamol-glucuronide, which was 3-fold higher than un-metabolised paracetamol (Tables 2 and 3).…”

Designing a TiO2-MoO3-BMIMBr nanocomposite by a solvohydrothermal method using an ionic liquid aqueous mixture: an ultra high sensitive acetaminophen sensor

“…5 Thus, the monitoring of POM in human serum, sweat, and water bodies are important for both human health and controlling environmental poisoning. 5 Numerous techniques such as high performance liquid chromatography, 6 UV spectrophotometry, 7 chemiluminescence 8 and titrimetry, 9 electrophorosis, 10 LC-MS 11 GC-MS 12 and flow injection 13 are available for the detection and determination of POM. Unfortunately, these techniques have several drawbacks and restrictions, such as being expensive and time-consuming.…”

Electrochemical Scaffold Based on Silver Phosphate Nanoparticles for the Quantification of Acetaminophen in Body Fluids and Pharmaceutical Formulations

“…To date, a variety of analytical tools have been developed for the quantification of ACAP in human fluids and pharmaceutical preparations such as LC-MS, 11 GC-MS, 12 HPLC, 13 spectrofluorometry, 14 chemiluminescence, 15 titrimetry, 16 and flow-injection 17 and FT-IR spectrophotometric analysis. 18 These methods are relatively expensive and time-consuming, require presample preparation, and have very complicated handling procedures.…”