The measurement of metanephrine (MN) and normetanephrine (NMN) in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the gold standard for the initial biochemical testing for pheochromocytomas and paragangliomas (PPGLs). Despite their high diagnostic value, there is a lack of consensus on the stability of MN and NMN in clinical specimens. This study aimed to analyze the stability of MN and NMN in both plasma and urine using LC-MS/MS under various conditions. Plasma and urine samples were prepared by spiking them with standard materials of MN and NMN. The samples were pretreated under solid phase extraction and analyzed using the LC-MS/MS system (Agilent Technologies, USA). In both plasma and urine specimens, MN and NMN were stable under the following conditions: (1) room temperature for 24 hours, (2) 4℃ for 8 days, (3) –20℃ for 8 days, and (4) –80℃ for 7 months. MN and NMN were stable after at least three cycles of the freeze and thaw process, and stable for 7 days in a container with dry ice. In this study, we comprehensively evaluated the stability of MN and NMN in plasma and urine and made recommendations to improve specimen handling to ensure reliable testing for PPGLs.

Keywords: Metanephrine, Normetanephrine, Plasma, Urine, Mass spectrometry, Pheochromocytoma, Paraganglioma, Stability