Evaluation of the 25-hydroxy vitamin D assay on a fully automated liquid chromatography mass spectrometry system, the Thermo Scientific Cascadion SM Clinical Analyzer with the Cascadion 25-hydroxy vitamin D assay in a routine clinical laboratory

Benton, Sally C; Tetteh, Godwin K.; Needham, Sarah-Jayne; Mücke, Jakob; Sheppard, Leanne; Alderson, Steven; Ruppen, Corinne; Curti, Maurus; Redondo, M.J.; Milan, Anna M.

doi:10.1515/cclm-2019-0834

Cited by 26 publications

(17 citation statements)

References 9 publications

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“…We have a census of around 50 patients admitted at any given time. This, in addition to the availability of Cascadion Analyzer [ 10 , 11 ], provided an opportunity to study 25-OH-D2 and 25-OH-D3 levels in COVID-19 positive patients and investigate their relationships to disease severity, as indicated by LOS, need for ventilation, and mortality, which may help resolve discordant results reported in previous studies.…”

Section: Introductionmentioning

confidence: 99%

25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients

et al. 2022

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Objectives Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes. Methods We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher’s exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used. Results COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53–18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95% CI]: 2.75 [1.10–6.90]). Conclusions There is an inverse relationship of 25-hydroxyvitamin D levels and hospital LOS for COVID-19 patients. Vitamin D status is a predictor for severity of outcomes. LCMS results are useful for assessing the odds of mortality and the need for ventilation during hospitalization.

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Section: Introductionmentioning

confidence: 99%

25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients

et al. 2022

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“…21 The last decade has seen strong efforts to develop fully automated random-access mass spectrometers. 22 The existing automated MS system(s) would likely benefit from IsoC use. In fact, any existing partially automated MS workflows might also be rendered random access capable with IsoC use, once a few standardized sets of reasonably fast extraction and chromatography conditions have been developed that suit many analytes.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Isotopic Distribution Calibration for Mass Spectrometry

et al. 2021

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Mass spectrometry (MS) is widely used in science and industry. It allows accurate, specific, sensitive, and reproducible detection and quantification of a huge range of analytes. Across MS applications, quantification by MS has grown most dramatically, with >50 million experiments/year in the USA alone. However, quantification performance varies between instruments, compounds, different samples, and within- and across runs, necessitating normalization with analyte-similar internal standards (IS) and use of IS-corrected multipoint external calibration curves for each analyte, a complicated and resource-intensive approach, which is particularly ill-suited for multi-analyte measurements. We have developed an internal calibration method that utilizes the natural isotope distribution of an IS for a given analyte to provide internal multipoint calibration. Multiple isotope distribution calibrators for different targets in the same sample facilitate multiplex quantification, while the emerging random-access automated MS platforms should also greatly benefit from this approach. Finally, isotope distribution calibration allows mathematical correction for suboptimal experimental conditions. This might also enable quantification of hitherto difficult, or impossible to quantify, targets, if the distribution is adjusted in silico to mimic the analyte. The approach works well for high resolution, accurate mass MS for analytes with at least a modest-sized isotopic envelope. As shown herein, the approach can also be applied to lower molecular weight analytes, but the reduction in calibration points does reduce quantification performance.

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“…Examples of automated systems that are currently available are the Shimadzu CLAM System 145 and ThermoFisher Scientific's Cascadion™ SM Clinical Analyzer 146 . The latter has been tested and compared with routine tests for Vitamin D and immunosuppressive drugs (cyclosporine A, sirolimus, tacrolimus, and everolimus) and showed excellent analytical performance 147,148 . For Vitamin D, all samples were within 10% of the reference concentrations, and for the immunosuppressive drugs, the mean deviation from the immunoassays was 17%–19%, 147,148 suggesting that automated LC–MS provides robust clinical data.…”

Section: Techniques and Challenges For Tdmmentioning

confidence: 99%

Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

et al. 2021

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Therapeutic drug monitoring (TDM) is typically referred to as the measurement of the concentration of drugs in patient blood. Although in the past, TDM was restricted to drugs with a narrow therapeutic range in order to avoid drug toxicity, TDM has recently become a major tool for precision medicine being applied to many more drugs. Through compensating for interindividual differences in a drug's pharmacokinetics, improved dosing of individual patients based on TDM ensures maximum drug effectiveness while minimizing side effects. This is especially relevant for individuals that present a particularly high intervariability in pharmacokinetics, such as newborns, or for critically/severely ill patients. In this article, we will review the applications for and limitations of TDM, discuss for which patients TDM is most beneficial and why, examine which techniques are being used for TDM, and demonstrate how mass spectrometry is increasingly becoming a reliable and convenient alternative for the TDM of different classes of drugs. We will also highlight the advances, challenges, and limitations of the existing repertoire of TDM methods and discuss future opportunities for TDM‐based precision medicine.

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Evaluation of the 25-hydroxy vitamin D assay on a fully automated liquid chromatography mass spectrometry system, the Thermo Scientific Cascadion SM Clinical Analyzer with the Cascadion 25-hydroxy vitamin D assay in a routine clinical laboratory

Cited by 26 publications

References 9 publications

25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients

25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients

Isotopic Distribution Calibration for Mass Spectrometry

Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

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