Determination of ropivacaine and its metabolites in patient urine: Advantage of liquid chromatography–tandem mass spectrometry over liquid chromatography–UV detection and liquid chromatography–mass spectrometry

Abstract

Analysis of urine samples from a clinical study of ropivacaine and its metabolites, 3-hydroxyropivacaine (3-OH-ropivacaine) and PPX, by an LC–UV method showed high concentrations of 3-hydroxyropivacaine, 2–50 times higher than expected. In the study, the patients were treated with a number of drugs in combination with ropivacaine. These drugs were paracetamol, lidocaine, fentanyl, morphine and trimethoprim. When the fraction of 3-hydroxyropivacaine was collected from LC–UV and analysed by LC–MS, only a high signal at mass number 291 [3-hydroxyropivacaine (MH +)] was observed. This observation indicates that it may be a drug or a metabolite having the same mass number as 3-hydroxyropivacaine and eluting at the same retention time on the LC system that gives a high signal in UV and MS detection. The examination of the drugs given showed that trimethoprim has the same molecular weight as 3-hydroxyropivacaine. The analysis of trimethoprim by LC–UV and LC–MS showed that under the given conditions it has the same retention time as 3-hydroxyropivacaine. The tuning of 3-hydroxyropivacaine and trimethoprim by MS–MS showed that both substances have the same precursor ions ( m/ z: 291) but different product ions ( m/ z: 126 and 123 for 3-hydroxyropivacaine and trimethoprim, respectively). This study shows that the use of LC–MS–MS may lead to more reliable results than LC–UV and LC–MS.