An LC-MS/MS method for creatine and creatinine analysis in paraquat-intoxicated patients |
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Authors: | Mukdawan Sukhang Anongphan Junkuy Nicholas Buckley Fahim Mohamed |
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Institution: | 1. Toxicology Unit, Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand;2. South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka;3. Clinical Pharmacology and Toxicology Research Group, Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia;4. Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka |
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Abstract: | AbstractA sudden increase in serum creatinine after paraquat intoxication has been reported in several clinical studies. However, this dramatic change of creatinine may be possibly due to an interconversion of creatine-creatinine in relation to paraquat toxicity. In order to investigate the creatine-creatinine relationship, a liquid chromatography tandem mass spectrometry in combination with electrospray ionization was developed and validated for simultaneous determination of creatine and creatinine in the serum. The chromatographic separation was achieved on a Gemini® C6-Phenyl column with a gradient elution consisting of 0.1% formic acid in ultrapure water and methanol as the mobile phase. The method yielded suitable levels of specificity and selectivity, and calibration curves of creatine and creatinine in serum were linear over the concentration range of 0.5–200?µg mL?1. The limit of quantification of both compounds was 0.5?µg mL?1, and the method was accurate within the recovery range of 96.23–102.75%, indicating the robustness of the method. The method was successfully applied to toxicological samples from paraquat-intoxicated patients, and the concentrations of creatine and creatinine were quantified. High creatine concentrations in serum samples were observed which may lead to high serum creatinine despite normal kidney function as creatine is converted to creatinine in proportion to its concentration. |
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Keywords: | Liquid chromatography tandem mass spectrometry creatine creatinine paraquat poisoning method validation method comparison matrix effect acute kidney injury kidney function nephrotoxicity |
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