title: Development and validation of liquid chromatography-tandem mass spectrometry method for quantification of plasma metanephrines for differential diagnosis of adrenal incidentaloma.
abstract: High-resolution imaging techniques have increased the detection rate of adrenal incidentaloma. We developed a method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection of plasma free metanephrine (MN) and normetanephrine (NMN) and evaluated its analytical performance and clinical efficacy in differential diagnosis of adrenal incidentaloma. After solid-phase extraction, chromatographic isolation of the analytes and internal standard was achieved by column elution in the LC-MS/MS system. The analytes were detected in multiple-reaction monitoring mode by using positive electrospray ionization: MN, transition m/z 180.1-->165.1; NMN, m/z 166.1-->134.1. This method was validated for linearity, precision, accuracy, lower limits of quantification and detection, extraction recovery, and the matrix effect. Plasma concentrations of MN and NMN of 14 patients with pheochromocytoma were compared with those of 17 healthy volunteers, 10 patients with essential hypertension, and 60 patients with adrenal adenoma. The assay's linear range was 0.04-50.0 and 0.08-100.0 nmol/L for MN and NMN, respectively. Assay imprecision was 1.86-7.50%. The accuracy ranged from -7.50% to 2.00%, and the mean recovery of MN and NMN was within the range 71.5-95.2%. Our LC-MS/MS method is rapid, accurate, and reliable and useful for differential diagnosis of adrenal incidentaloma.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sae Mi
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Green Cross Laboratories, Seoul, Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyeon Ju
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Cho
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Woo
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyung Doo
authors.initials: HD
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. suddenbz@skku.edu.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003937:Diagnosis, Differential; D006801:Humans; D008676:Metanephrine / Q000097:blood* / Q000302:isolation & purification; D009647:Normetanephrine / Q000097:blood; D010673:Pheochromocytoma / Q000175:diagnosis; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D009647:Normetanephrine; D008676:Metanephrine
keywords: Mass spectrometry; Metanephrines; Pheochromocytoma; Plasma; Validation