Determination of N-acetylcysteine in human plasma by liquid chromatography coupled to tandem mass spectrometry.
An analytical method for the determination of total N-acetylcysteine in human plasma has been developed, validated and applied to the analysis of samples from a phase I clinical trial. The analytical method consists of plasma digestion with dithiothreitol in order to reduce all the oxidized forms of N-acetylcysteine, and extraction with ethyl acetate followed by determination of levels by an LC-MS-MS method. The intra- and inter-assay precision and accuracy of this technique were good and the limit of quantitation was 50 ng/ml of plasma. The concentration working range was established between 50 ng/ml and 1000 ng/ml. This method has been used in the analysis of approximately 800 human plasma samples from a clinical study with 24 volunteers; the precision of the quality controls was in the range 8.7 to 13.4% and the accuracy was in the range -5.9 to 8.5%, expressed as the RSD and the relative error, respectively.
Celma
C
C
Metabolism and Pharmacokinetics Department, Ipsen Pharma, Sant Feliu de Llobregat (Barcelona), Spain. carles.celma@beaufour-ipsen.com
Allué
J A
JA
Pruñonosa
J
J
Peraire
C
C
Obach
R
R
D000111:Acetylcysteine / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000111:Acetylcysteine