Iothalamate quantification by tandem mass spectrometry to measure glomerular filtration rate. 2010

Jesse C Seegmiller, and Bradley E Burns, and Abdul H Fauq, and Naveen Mukhtar, and John C Lieske, and Timothy S Larson
Department of Laboratory Medicine and Pathology, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.

BACKGROUND Glomerular filtration rate (GFR) can be determined by measuring renal clearance of the radiocontrast agent iothalamate. Current analytic methods for quantifying iothalamate concentrations in plasma and urine using liquid chromatography or capillary electrophoresis have limitations such as long analysis times and susceptibility to interferences. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to overcome these limitations. METHODS Urine and plasma samples were deproteinized using acetonitrile and centrifugation. The supernatant was diluted in water and analyzed by LC-MS/MS using a water:methanol gradient. We monitored 4 multiple reaction monitoring transitions: m/z 614.8-487.0, 614.8-456.0, 614.8-361.1, and 614.8-177.1. We compared the results to those obtained via our standard capillary electrophoresis (CE-UV) on samples from 53 patients undergoing clinical GFR testing. RESULTS Mean recovery was 90%-110% in both urine and plasma matrices. Imprecision was <or=15% for the m/z 614.8-487.0 and 614.8-456.0 transitions over a 10-day period at 1 mg/L. Method comparison for 159 patient samples (53 clearances) provided the following Passing-Bablok regressions: plasma iothalamate LC-MS/MS (y) vs CE-UV (x), y = 0.99x + 0.36; urine iothalamate LC-MS/MS vs CE-UV, y = 1.01x + 0.31; corrected GFR LC-MS/MS vs CE-UV, y = 1.00x + 0.00. Interfering substances prevented accurate iothalamate quantification by CE-UV in 2 patients, whereas these samples could be analyzed by LC-MS/MS. CONCLUSIONS Iothalamate can be quantified by LC-MS/MS for GFR measurement. This method circumvents potential problems with interfering substances that occasionally confound accurate GFR determinations.

UI MeSH Term Description Entries
D007483 Iothalamic Acid A contrast medium in diagnostic radiology with properties similar to those of diatrizoic acid. It is used primarily as its sodium and meglumine (IOTHALAMATE MEGLUMINE) salts. Iotalamic Acid,Methalamic Acid,Angio-Conray,Conray 420,Iodothalamate,Iothalamate,Iothalamic Acid, Calcium (2:1) Salt,Iothalamic Acid, Monosilver (1+) Salt,Iothalamic Acid, Monosodium Salt,Iothalamic Acid, Monosodium Salt, Dimer,Lopamidol,Sodium Iothalamate,Acid, Iotalamic,Acid, Iothalamic,Acid, Methalamic,Angio Conray,AngioConray,Iothalamate, Sodium
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D019075 Electrophoresis, Capillary A highly-sensitive (in the picomolar range, which is 10,000-fold more sensitive than conventional electrophoresis) and efficient technique that allows separation of PROTEINS; NUCLEIC ACIDS; and CARBOHYDRATES. (Segen, Dictionary of Modern Medicine, 1992) Capillary Zone Electrophoresis,Capillary Electrophoreses,Capillary Electrophoresis,Capillary Zone Electrophoreses,Electrophoreses, Capillary,Electrophoreses, Capillary Zone,Electrophoresis, Capillary Zone,Zone Electrophoreses, Capillary,Zone Electrophoresis, Capillary

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