Determination of Ketone Bodies in Blood by Headspace Gas Chromatography-Mass Spectrometry

Holm, Karen Marie Dollerup; Línnet, Kristían; Rasmussen, Brian Schou; Pedersen, Anders Just

doi:10.1093/jat/34.9.549

Cited by 8 publications

(3 citation statements)

References 22 publications

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“…Next, the mass spectrometry part of GC-MS ionizes the molecules to form a unique fragmentation pattern, which is used to identify molecules with 1Da precision. GC-MS has long been considered the most valid and accurate technique with regard to ketone metrics [19], and the importance of establishing accurate measurements of circulating ketone bodies lies in its potential to help to better discern between states of nutritional ketosis (read as 0.5-3 mM when using a blood meter) and pathological ketosis, otherwise known as ketoacidosis, a state that exceeds nutritional ketosis by 5-10-fold greater values of βHB [20,21]. Ketoacidosis is induced either by uncontrolled type 1 diabetes mellitus with a complete lack of insulin signaling or extreme alcohol consumption paired with severe caloric restriction [20,21].…”

Section: Introductionmentioning

confidence: 99%

Discrepancy of Beta-Hydroxybutyrate Measurements between a Blood Meter and GC-MS Methods in Healthy Humans

Holland-Winkler,

Moore,

Ansley

et al. 2023

Muscles

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Ketone salt (KS) supplementation induces temporary nutritional ketosis to achieve potential exercise performance and health benefits. Racemic KS includes both D/L isomers of β-hydroxybutyrate, yet commercially available measurement devices (i.e., blood meters) only measure the D variant. The aim of this study was to investigate the efficacy of a blood meter to measure serum β-hydroxybutyrate in comparison with gas chromatography–mass spectrometry (GC-MS) before and 30 min after consuming a placebo or racemic KS. In this triple-blinded cross-over study, 16 healthy adults were administered either a placebo or KS drink, and the circulating β-hydroxybutyrate concentration was measured at baseline (PRE) and 30 min following consumption (POST) using a blood ketone meter and by GC-MS. Compared to the placebo, both GC-MS and the blood meter obtained significantly greater β-hydroxybutyrate levels from PRE to POST time-points after consuming KS. Additionally, GC-MS results showed significantly higher levels of β-hydroxybutyrate with both the placebo and KS at PRE and POST time-points, as compared to the blood meter. These results indicate that (1) even in the absence of KS, the blood meter yields significantly lower β-hydroxybutyrate values than GC-MS, and (2) the inability of the blood meter to measure L-β-hydroxybutyrate values POST KS warrants the further development of publicly available ketone measurement apparatuses.

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Section: Introductionmentioning

confidence: 99%

Discrepancy of Beta-Hydroxybutyrate Measurements between a Blood Meter and GC-MS Methods in Healthy Humans

Holland-Winkler,

Moore,

Ansley

et al. 2023

Muscles

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“…Moreover, 15–20% of adult and 30–40% of adolescent diabetic patients with undiagnosed diabetes, first present with DKA [ 2 ]. DKA is characterized by an increase in ketone bodies as cells become unable to transport and use glucose [ 2 , 5 , 6 ]. In the emergency department (ED), the key laboratory findings of DKA generally include glucose levels greater than 250 mg/dL, blood pH less than 7.3, serum bicarbonate less than 18 mmol/L, anion gap less than 10, and the presence of urine and serum ketones.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of Interstitial Fluid Ketone Monitoring with Microneedles

Taylor

Baca

2022

Metabolites

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Diabetic ketoacidosis (DKA) is one of the most dangerous and costly complications of diabetes, accounting for approximately 50% of deaths in diabetic individuals under 24 years. This results in over 130,000 hospital admissions yearly and costs the USA over USD 2.4 billion annually. Earlier diagnosis, treatment, and management of DKA are of critical importance to achieving better patient outcomes and preventing prolonged hospital admissions. Diabetic patients undergoing stress from illness or injury may not recognize early ketosis and often present advanced ketoacidosis, requiring intensive care admission. We have recently developed a microneedle-based technology to extract dermal interstitial fluid (ISF) from both animals and humans, which could enable wearable sensors to rapidly detect ketosis. Metabolite concentrations in ISF may differ in urine and blood and could likely represent local metabolic conditions in the surrounding tissue. Development of a wearable ketone detector will require an understanding of ketone concentrations and kinetics in ISF. Here, we report data that is first of its kind, with regard to the ketone concentrations present in the dermal ISF of rats, their correlation to blood, and the possible impact on the development of a wearable ISF “early warning system” to prevent morbidity from DKA. We extracted ISF, using minimally invasive microneedle arrays, from control Sprague Dawley rats and 17 h fasted rats. ISF and blood ketone levels were measured using a common glucose/ketone meter and strips. Local tissue concentrations of glucose were similar to those of blood, with an average blood to ISF glucose ratio of 0.99 ± 0.15 mg/dL. ISF ketones (0.4 ± 0.3 mM) were significantly higher (p = 4.2 × 10−9), compared with blood ketones (0.0 ± 0.0 mM). Although the fasted animals had slightly higher ISF ketones (1.3 ± 1.1 mM) compared with blood ketones (1.0 ± 1.0 mM), the difference was not significant (p = 0.3). This suggests ISF could possibly be useful as a surrogate for blood when determining ketone levels within a clinical setting.

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“…Although ketone bodies have been studied for decades, more sensitive analytical methods are needed with high selectivity and specificity. Head-space gas chromatography has been applied in several cases for indirect determination of beta-hydroxy butyrate (BHB) in plasma and blood samples (Kimura et al, 1985;Felby et al, 1994;Holm et al, 2010). GC-MSD derivatization has also been reported for the determination of BHB in blood and plasma (Nissen et al, 1990;Hassan et al, 2009;Elliott et al, 2010;Hur et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Plasma Lactate, Pyruvate, and Ketone Bodies following tert-Butyldimethylsilyl Derivatization using GC-MS-SIM

Yoon

2015

BSL

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Lactate and ketone bodies are considered biological markers for ketosis and several inherited metabolic disorders. In the current study, the specific ratios of lactate and ketone bodies as analytical tools for differential diagnosis of various lactic acidosis were devised. The study included a protein precipitation step following tert-butyldimethylsilyl derivatisation. Total run time was approximately 30 min including sample preparation and GS/MS analysis. The limits of detection were below 0.1 pg/mL over the targeted 4 analytes. The calibration curve was linear over the concentration range of 0.001~ 250 μg/mL for pyruvate, beta-hydroxybutyrate, and acetoacetate (R 2 > 0.99). Inter-day accuracy and precision were 87.7~94.8% with RSD of 2.5~5.7% at 2 levels. Absolute recoveries (%) of target analytes were 87.0~98.4%. The method was validated for the quantification of lactate and ketone bodies for differentiation of lactic acidosis.

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Determination of Ketone Bodies in Blood by Headspace Gas Chromatography-Mass Spectrometry

Cited by 8 publications

References 22 publications

Discrepancy of Beta-Hydroxybutyrate Measurements between a Blood Meter and GC-MS Methods in Healthy Humans

Discrepancy of Beta-Hydroxybutyrate Measurements between a Blood Meter and GC-MS Methods in Healthy Humans

Feasibility of Interstitial Fluid Ketone Monitoring with Microneedles

Simultaneous Determination of Plasma Lactate, Pyruvate, and Ketone Bodies following tert-Butyldimethylsilyl Derivatization using GC-MS-SIM

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