Development and validation of a simple, fast and sensitive liquid chromatography-tandem mass spectrometry method to establish reference intervals for 24-h urinary free normetanephrine, metanephrine and methoxytyramine
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ABSTRACT:
SUBMITTER: Song Y
PROVIDER: S-EPMC10840320 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Accumulating evidence links higher circulating asymmetric dimethylarginine (ADMA) to greater risk of cardiovascular disease (CVD). Relatively small differences in ADMA concentrations between healthy individuals and those with disease underscore the need to formulate reference intervals that may aid risk stratification of individuals. METHODS:We formulated reference intervals for plasma ADMA concentrations using a community-based reference sample from the Framingham Offspring Study consisting of 1126 nonsmoking individuals [mean (SD) age 56 (9) years; 60% women] who were free of clinical CVD, hypertension, diabetes, and obesity and who attended a routine examination at which ADMA was assayed. ADMA concentrations were determined using a validated tandem mass spectrometry-liquid chromatography assay. RESULTS:In the study sample, the mean ADMA concentration was 0.52 (0.11) micromol/L, and the reference limits were 0.311 and 0.732 (2.5th and 97.5th percentile). The sex-specific reference limits were 0.310 and 0.745 in men and 0.313 and 0.721 micromol/L in women. In multivariable regression analysis, ADMA plasma concentrations were positively correlated with age and total plasma homocysteine (both P < 0.001). CONCLUSIONS:Reference limits calculated for circulating ADMA in our large community-based healthy reference sample confirm the previous observation of a relatively narrow distribution of concentrations. This suggests a tight physiological control of ADMA plasma concentrations, presumably by dimethylarginine dimethylaminohydrolase (DDAH) metabolism of ADMA.
| S-EPMC3794429 | biostudies-literature
Project description:BackgroundAge, race, and analytic method influence levels of blood amino acids, of which reference intervals are required for the diagnosis and management of inherited metabolic disorders.ObjectivesTo establish age-specific reference intervals for blood amino acids in Thai pediatric population measured by liquid chromatography tandem mass spectrometry (LC-MS/MS).MethodsA cross-sectional study of 277 healthy children from birth to 12 years was conducted. Anthropometric, clinical, and dietary information were recorded. Dried blood spots on a filtered paper were used for measurement by derivatized LC-MS/MS. Factors that might affect amino acids such as fasting time and dietary intake were analyzed using quantile regression analysis.ResultsLevels of thirteen blood amino acids were reported as median and interval from 2.5th-97.5th percentiles. Compared with those of Caucasian, most blood amino acid levels of Thai children were higher. Compared with a previous study using HPLC in Thai children, many amino acid levels are different. Glycine, alanine, leucine/isoleucine, and glutamic acid sharply decreased after birth. Citrulline, arginine, and methionine stayed low from birth throughout childhood, whereas phenylalanine was at middle level and slightly increased during preadolescence.ConclusionReference intervals of age-specific blood amino acids using LC-MS/MS were established in the Thai pediatric population. They diverge from previous studies, substantiating the recommendation that, for the optimal clinical practice, age-specific reference intervals of amino acids should be designated for the particular population and analysis method.
| S-EPMC5960525 | biostudies-literature
Project description:ObjectiveMeasurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing.MethodsAfter validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed.ResultsPerformance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples.ConclusionsThe reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile.Significance statementQuantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.
| S-EPMC10762560 | biostudies-literature
Project description: Not available
| S-EPMC7249713 | biostudies-literature
Project description:The glycoform of a therapeutic monoclonal antibody (mAb) has a significant impact on its effector function as well as its safety and pharmacokinetics. Glycoform heterogeneity is influenced by various factors, including the producing cells and cell culture processes. Therefore, accurate glycoform characterization is essential for drug design, process optimization, manufacturing, and quality control of therapeutic mAbs. In this study, we developed a fast, quantitative, and highly sensitive analytical platform for glycan profiling by supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) and applied the technique to the glycan structural analysis of mAbs. To achieve both the highest sensitivity and the most comprehensive glycan profiling, we integrated our energy-resolved oxonium ion monitoring (Erexim) method with SFC-MS to construct a new SFC-Erexim technology. An 8 min analysis of bevacizumab, nivolumab, ramucirumab, rituximab, and trastuzumab by SFC-Erexim detected a total of 102 glycoforms, with a detection limit of 5 attomoles. The dynamic range of glycan abundance was over 6 orders of magnitude for bevacizumab analysis by SFC-Erexim compared to 3 orders of magnitude for conventional fluorescence HPLC analysis. This method revealed the glycan profile characteristics and lot-to-lot heterogeneity of various therapeutic mAbs. We were also able to detect a series of structural variations in pharmacologically important glycan structures. The SFC-MS-based glycoform profiling method will provide an ideal platform for the in-depth analysis of precise glycan structure and abundance.
| S-EPMC9685587 | biostudies-literature
Project description:This study aimed to describe the latest 25-hydroxyvitamin D (25(OH)D) status of the South Korean population aged ≥ 20 years using 25(OH)D concentrations measured by liquid chromatography-tandem mass spectrometry and to determine the factors associated with total 25(OH)D concentrations. This cross-sectional, retrospective study consecutively selected 119,335 subjects with a median age of 57 (20-101) years who underwent health checkups among 13 Korean cities during 2017-2022. The total 25(OH)D concentration was 54.5 ± 24.0 nmol/L (mean ± SD). The 7.6%, 47.5%, and 82.9% of participants had 25(OH)D less than 25, 50, and 75 nmol/L, respectively. The prevalence of 25(OH)D deficiency (<25 nmol/L) was higher in females than in males (8.9% vs. 6.1%) and varied between age groups, decreasing in older subjects. Those aged 20-29 years had the highest prevalence of 25(OH)D deficiency (23.0% in females and 20.1% in males), which also varied between cities. In the adjusted model, female sex, older age, summer and autumn seasons, lower body mass index (<25 kg/m2), and lower high-sensitivity C-reactive protein concentration (<1 mg/L) were associated with higher total 25(OH)D concentrations. This study could provide an exact understanding of the status of vitamin D and help devise strategies to prevent vitamin D deficiency among the Korean population.
| S-EPMC10934696 | biostudies-literature
Project description:Background: Metabolomics serves as a very useful tool for elucidating disease mechanisms and identifying biomarkers. Establishing reference intervals (RIs) of metabolites in a healthy population is crucial to the application of metabolomics in life sciences and clinics. Methods: We enrolled 615 healthy Chinese adults aged between 21 and 85 years. Their health status was ascertained through clinical examinations, biochemical parameters, and medical history. Targeted metabolomics and lipidomics analyses were applied to quantify 705 metabolites and lipids in the serum, establishing RIs and investigating the effect of sex and age on the metabolome and lipidome. Results: This study is the first large-scale effort in China to establish RIs for metabolites in the apparently healthy population. We found that most of the sex-related metabolites, including amino acids, acyl-carnitines and triacylglycerols, had higher concentrations in males, while the other sex-related lipids showed higher concentrations in females. Most of the age-related metabolites increased with age, including those associated with protein synthesis, nitric oxide synthesis, energy metabolism, and lipid metabolism. Conclusions: This study gives the reference intervals of the healthy Chinese metabolome and lipidome and their relationship with sex and age, which facilitates life sciences and precision medicine, especially for disease research and biomarker discovery.
| S-EPMC11857409 | biostudies-literature
Project description:Celiac disease (CD) is an inflammatory disorder of the upper small intestine caused by the ingestion of storage proteins (prolamins and glutelins) from wheat, barley, rye, and, in rare cases, oats. CD patients need to follow a gluten-free diet by consuming gluten-free products with gluten contents of less than 20 mg/kg. Currently, the recommended method for the quantitative determination of gluten is an enzyme-linked immunosorbent assay (ELISA) based on the R5 monoclonal antibody. Because the R5 ELISA mostly detects the prolamin fraction of gluten, a new independent method is required to detect prolamins as well as glutelins. This paper presents the development of a method to quantitate 16 wheat marker peptides derived from all wheat gluten protein types by liquid chromatography tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The quantitation of each marker peptide in the chymotryptic digest of a defined amount of the respective reference wheat protein type resulted in peptide-specific yields. This enabled the conversion of peptide into protein type concentrations. Gluten contents were expressed as sum of all determined protein type concentrations. This new method was applied to quantitate gluten in wheat starches and compared to R5 ELISA and gel-permeation high-performance liquid chromatography with fluorescence detection (GP-HPLC-FLD), which resulted in a strong correlation between LC-MS/MS and the other two methods.
| S-EPMC5806900 | biostudies-literature
Project description:BackgroundDespite the extensive research on data mining algorithms, there is still a lack of a standard protocol to evaluate the performance of the existing algorithms. Therefore, the study aims to provide a novel procedure that combines data mining algorithms and simplified preprocessing to establish reference intervals (RIs), with the performance of five algorithms assessed objectively as well.MethodsTwo data sets were derived from the population undergoing a physical examination. Hoffmann, Bhattacharya, Expectation Maximum (EM), kosmic, and refineR algorithms combined with two-step data preprocessing respectively were implemented in the Test data set to establish RIs for thyroid-related hormones. Algorithm-calculated RIs were compared with the standard RIs calculated from the Reference data set in which reference individuals were selected following strict inclusion and exclusion criteria. Objective assessment of the methods is implemented by the bias ratio (BR) matrix.ResultsRIs of thyroid-related hormones are established. There is a high consistency between TSH RIs established by the EM algorithm and the standard TSH RIs (BR = 0.063), although EM algorithms seems to perform poor on other hormones. RIs calculated by Hoffmann, Bhattacharya, and refineR methods for free and total triiodo-thyronine, free and total thyroxine respectively are close and match the standard RIs.ConclusionAn effective approach for objectively evaluating the performance of the algorithm based on the BR matrix is established. EM algorithm combined with simplified preprocessing can handle data with significant skewness, but its performance is limited in other scenarios. The other four algorithms perform well for data with Gaussian or near-Gaussian distribution. Using the appropriate algorithm based on the data distribution characteristics is recommended.
| S-EPMC10152698 | biostudies-literature
Project description:Background and objectivesVery long-chain fatty acyl-lysophosphatidylcholines (VLCFA-LysoPCs) are measured in dried blood spots (DBS) for identifying X-linked adrenoleukodystrophy (X-ALD) and other inherited peroxisomal disorders. Our study aimed to establish age- and gender-specific reference intervals for a panel of LysoPCs measured by tandem mass spectrometry in DBS.MethodsLysoPCs (26:0-, 24:0-, 22:0- and 20:0-LysoPCs) were estimated by flow injection analysis-tandem mass spectrometry (FIA-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods in 3.2 mm blood spots of 2689 anonymized, putative normal subjects (1375 males, and 1314 females) aged between 2 days and 65 years. Samples were divided into groups: Neonates (0-1month), Infants (>1m-1year), Children and Adolescents (>1-18years), and Adults (>18years). Reference intervals were determined using the percentile approach and represented as the median with the 1st and 99th percentile lower and upper limits.ResultsThe percentage coefficient of variation (CV) for repeatability assays of internal and external quality control samples were within acceptable limits. Significant differences (P <0.0001, P <0.01) were observed in the concentrations of 26:0-, 24:0-, 22:0- and 20:0-LysoPCs and their ratios, 26:0/22:0-, 24:0/22:0-, 26:0/20:0-and 24:0/20:0-LysoPC in neonates and infants when compared to children, adolescents, and adults. Levels of 26:0-, 24:0- and 22:0-LysoPCs decreased, whereas 20:0-LysoPC increased with age. There were no significant gender-based differences in the concentration of LysoPCs.ConclusionWe established age- and gender-specific reference intervals for a panel of LysoPCs in DBS. These reference values would be helpful when interpreting LysoPC values in DBS during screening for X-ALD and other peroxisomal disorders.
| S-EPMC9813575 | biostudies-literature