Quantifying MMA by SLE LC-MS/MS: Unexpected challenges in assay development.

Abstract:

OBJECTIVES:Analysis of serum/plasma methylmalonic acid (MMA) is important for the diagnosis and management of methylmalonic acidemia in pediatric populations. This work focuses on developing and validating a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to monitor methylmalonic acidemia using a simple method preparation. DESIGN AND METHODS:MMA and stable isotope labeled d3-MMA was extracted using supported liquid extraction (SLE). Assay imprecision, bias, linearity, recovery and carryover were determined. The relationship between MMA and propionyl acylcarnitine (C3-acylcarnitine) was also evaluated using historical paired results from 51 unique individuals. RESULTS:Baseline separation between MMA and succinic acid was completed in 7min. The assay was linear from 0.1 to 500μM. The intra-day and inter-day imprecision CV ranged from 4.1 to 13.2% (0.3 to 526μM) and 5.0 to 15.7% (0.3 to 233μM), respectively. Recovery ranged from 93 to 125%. The correlation with a national reference laboratory LC-MS/MS assay showed a Deming regression of 1.026 and intercept of -1.335. Carryover was determined to be <0.04%. Patient-specific correlation was observed between MMA and C3-acylcarnitine. CONCLUSION:This report describes the first LC-MS/MS method using SLE for MMA extraction. In addition, we illustrate the challenges encountered during this method development that should be assessed and resolved by any laboratory implementing a SLE LC-MS/MS assay designed to quantify analytes across several orders of magnitude.

journal_name

Clin Biochem

journal_title

Clinical biochemistry

authors

Lo SY,Gordon C,Sadilkova K,Jack RM,Dickerson JA

doi

10.1016/j.clinbiochem.2016.05.010

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

967-72

issue

13-14

eissn

0009-9120

issn

1873-2933

pii

S0009-9120(16)30058-3

journal_volume

49

pub_type

杂志文章
  • A sensitive and rapid mass spectrometric method for the simultaneous measurement of eight steroid hormones and CALIPER pediatric reference intervals.

    abstract:OBJECTIVES:To develop an accurate assay and establish the normal reference intervals for serum cortisol, corticosterone, 11-deoxycortisol, androstenedione, 21-hydroxyprogesterone, testosterone, 17-hydroxyprogesterone, and progesterone. These steroids are commonly used as biomarkers for the diagnosis and monitoring of e...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2013.01.002

    authors: Kyriakopoulou L,Yazdanpanah M,Colantonio DA,Chan MK,Daly CH,Adeli K

    更新日期:2013-05-01 00:00:00

  • Genetic risk factors for renal failure among north Indian ESRD patients.

    abstract:OBJECTIVES:Angiotensin converting enzyme (ACE), G-Protein couple receptor (G-Prot), endothelial nitric oxide synthase (ecNOS), Leptin -2548G/A and uncoupling protein (UCP2) are potent regulators of intra renal hemodynamics and may be the causative factors contributing to the deterioration of renal functions. In recent ...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2008.01.009

    authors: Tripathi G,Sharma RK,Baburaj VP,Sankhwar SN,Jafar T,Agrawal S

    更新日期:2008-05-01 00:00:00

  • Changes in serum enzyme activity after transcatheter arterial embolization for hepatic neoplasm.

    abstract::We assayed serum levels of certain enzymes and tumor markers in patients after transcatheter arterial embolization (TAE) to evaluate the effectiveness of this treatment. Twenty patients had hepatocellular carcinoma and two patients had metastases to the liver from colon cancer. Assays were first done immediately after...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/0009-9120(87)90011-7

    authors: Yoshikawa C,Shimojo N,Naka K,Akai T,Okuda K,Kaminou T,Yamada T,Nakatsuka H

    更新日期:1987-12-01 00:00:00

  • Correlation of endothelin 1 plasma levels with plasma antioxidant capacity in elderly patients treated for hypertension.

    abstract:UNLABELLED:Experimental studies confirmed that reactive oxygen species increase endothelin-1 (ET-1) synthesis, and modulate ET-1 signaling pathway resulting in vasoconstriction and vascular remodeling. The aim of this study was to evaluate the relationship between plasma ET-1 concentration and antioxidant status in pat...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2008.11.002

    authors: Skalska AB,Pietrzycka A,Stepniewski M

    更新日期:2009-03-01 00:00:00

  • 1,5-anhydroglucitol monitoring in diabetes: a mass balance perspective.

    abstract::1,5-anhydroglucitol (AG) is a nonmetabolizable glucose analogue found in plasma due to ingestion. The normal steady-state concentration can be dramatically decreased by inhibition of tubular reabsorption during periods of hyperglycemia. For this reason, monitoring of AG has been plausibly advocated for detection of pe...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinbiochem.2008.08.086

    authors: Nerby CL,Stickle DF

    更新日期:2009-02-01 00:00:00

  • Utility of CA 15-3 and CEA in monitoring breast cancer patients with bone metastases: special emphasis on "spiking" phenomena.

    abstract:OBJECTIVES:CA 15-3 and CEA are considered useful tumor markers in monitoring breast cancer patients. This study was undertaken to specifically evaluate the transient elevations in these markers that are observed during systemic treatment for metastatic disease. This phenomenon has been termed "spiking." DESIGN AND MAT...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/s0009-9120(96)00133-6

    authors: Yasasever V,Dinçer M,Camlica H,Karaloğlu D,Dalay N

    更新日期:1997-02-01 00:00:00

  • Blood levels of polycyclic aromatic hydrocarbons in children and their association with oxidative stress indices: an Indian perspective.

    abstract:BACKGROUND:Polycyclic aromatic hydrocarbons (PAHs), some ubiquitous environmental contaminants are capable to cause oxidative stress, during its metabolism. It is believed that many diseases that have a common origin in oxidative stress begin in childhood. Considering oxidative stress evolved during PAHs metabolism as ...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2007.11.017

    authors: Singh VK,Patel DK,Jyoti,Ram S,Mathur N,Siddiqui MK

    更新日期:2008-02-01 00:00:00

  • Background hCG in non-pregnant individuals: need for more sensitive point-of-care and over-the-counter pregnancy tests.

    abstract:BACKGROUND:Currently, 20 IU/L is the accepted sensitivity of over-the-counter (OTC) hCG pregnancy tests, and the only sensitivity permitted for point of care (POC) tests. These sensitivity limitations cause significant numbers of false-negative tests, which mislead women and cause them to avoid precautions needed to av...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2008.09.107

    authors: Cole LA,Ladner DG

    更新日期:2009-02-01 00:00:00

  • Galactosemia: screening and diagnosis.

    abstract::Galactose is normally metabolized to glucose through the coordinated activities of three enzymes: galactokinase, galactose-1-phosphate uridyl transferase (GALT), and uridine diphospho-glucose 4-epimerase (epimerase). High concentrations of galactose and their metabolites are toxic to mammals. Hereditary deficiencies o...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/0009-9120(91)80003-l

    authors: Beutler E

    更新日期:1991-08-01 00:00:00

  • A sensitive method for the determination of hydrochlorothiazide in serum by high pressure liquid chromatography.

    abstract::A high pressure liquid chromatographic method for the determination of hydrochlorothiazide in serum has been elaborated and verified in a blood level study in normal individuals given a single oral dose of 50 mg hydrochlorothiazide. Based on 5 ml of serum, the limit of detection of the method is 2 ng/ml. ...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/s0009-9120(78)90434-4

    authors: Robinson WT,Cosyns L

    更新日期:1978-08-01 00:00:00

  • A correlation of serum bile acid levels with conventional biochemical parameters in the assessment of hepatobiliary dysfunctions.

    abstract::In hepatobiliary disease, the level of bile acids in the peripheral circulation is greatly increased due to impaired liver function. It has been suggested that serum bile acids are of greater value in confirming hepatobiliary dysfunction than the currently assayed conventional biochemical parameters. Fifty patients wi...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/s0009-9120(81)91052-3

    authors: Jarzabek JI,Kampa IS

    更新日期:1981-12-01 00:00:00

  • Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients.

    abstract:OBJECTIVES:Breast cancer is the most common malignancy among Egyptian women. The aim of this study is to evaluate the role of both telomerase and TPS estimation in assessment of breast cancer. METHODS:The study included 40 patients with breast cancer, and 20 patients with benign breast diseases. Telomerase activity in...

    journal_title:Clinical biochemistry

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0009-9120(01)00253-3

    authors: Kassim SK,Fawzy H,El Rassad MM,Khalil FK,Khalifa A

    更新日期:2001-09-01 00:00:00

  • Biochemistry and clinical chemistry of vitamin B12 transport and the related diseases.

    abstract::This review focusses on research performed by the author and coworkers. The absorption, turnover and excretion of cobalamin and the pathogenesis of cobalamin deficiency states are described and the laboratory tests used to diagnose these states are discussed. Topics dealt with in detail include: overall turnover, dail...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/s0009-9120(84)90279-0

    authors: Gräsbeck R

    更新日期:1984-04-01 00:00:00

  • Efficacy and safety of prasugrel in acute coronary syndrome patients.

    abstract::Ischemic heart disease is the primary cause of death worldwide. The pathophysiological process of cardiovascular diseases is linked to atheromatous plaque formation, while plaque rupture releases thrombogenic elements, which lead to activation of platelets, blood clotting and formation of thrombi. Platelet inhibitors ...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinbiochem.2014.03.005

    authors: Nanau RM,Delzor F,Neuman MG

    更新日期:2014-05-01 00:00:00

  • Changes in serum histologic surrogate markers and procollagen III N-terminal peptide as independent predictors of HBeAg loss in patients with chronic hepatitis B during entecavir therapy.

    abstract:OBJECTIVES:The aims of this study were to determine the changes in serum histologic surrogate markers and to identify the serum markers predicting treatment response in patients with chronic hepatitis B (CHB) during entecavir treatment. DESIGN AND METHODS:Sixty CHB patients who received entecavir for 12 months were in...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2011.09.023

    authors: Koo JH,Lee MH,Kim SS,Kim DH,Kim IS,Lee KM,Yoo BM,Lee KJ,Kim JH,Cho SW,Cheong JY

    更新日期:2012-01-01 00:00:00

  • Comparative study of respiratory burst induced by phorbol ester and zymosan in human granulocytes.

    abstract:OBJECTIVES:We have comparatively evaluated respiratory burst and some steps of its signaling in human granulocytes towards different stimuli. MATERIALS AND METHODS:An alternative method to remove erythrocytes by dextran differential sedimentation was employed. Respiratory burst (RB) was assessed in a flow cytometer by...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2005.10.005

    authors: Lunardi F,Lima JH,Assreuy J

    更新日期:2006-01-01 00:00:00

  • Interaction of common sequence variants and selected risk factors in determination of HDL cholesterol levels.

    abstract:OBJECTIVES:The aim of our study was to assess the association of common sequence variants, and selected interactions, with HDL-c plasma levels. DESIGN AND METHODS:We analysed 743 individuals (340 men and 403 women) with high mean triglyceride and LDL-c levels. The association of five polymorphic sites (ABCA1 g.1051G>A...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2010.04.001

    authors: Katerina H,Michaela S,Michal V,Helena S,Jana Z,Jaroslav H,Richard C

    更新日期:2010-06-01 00:00:00

  • Preanalytics in urinalysis.

    abstract::Urine contains an enormous amount of information. Well-standardized procedures for collection, transport, sample preparation and analysis should become the basis of an effective diagnostic strategy for urinalysis. As reproducibility of urinalysis has been greatly improved due to recent technological progress, preanaly...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinbiochem.2016.10.016

    authors: Delanghe JR,Speeckaert MM

    更新日期:2016-12-01 00:00:00

  • Biochemical and biological aspects of the plasminogen activation system.

    abstract::Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolys...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/0009-9120(90)90601-p

    authors: Mayer M

    更新日期:1990-06-01 00:00:00

  • Toxic risks of inappropriate therapy.

    abstract::Drug therapy may produce toxicity. Patient individuality or drug interactions account for many cases of poisoning, but other factors such as genetic predisposition, drug contamination or human error are also known causes. Examples of various types of drug poisoning are given, illustrating the role of the clinical chem...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,评审

    doi:10.1016/0009-9120(90)90507-q

    authors: Stewart MJ

    更新日期:1990-02-01 00:00:00

  • An immunoassay for qualitative estimation of collagenase activity in mammalian tissues.

    abstract::Collagen, the most abundant protein of the mammalian body, is specifically degraded by collagenase. Collagenase activity and subsequent collagen degradation are the main aspects of essential biological processes such as bone remodeling, tissue repair and wound healing. Measurement of collagenase activity is of interes...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/s0009-9120(05)80002-5

    authors: Chakraborty A,Eghbali M

    更新日期:1991-12-01 00:00:00

  • Preeclampsia-associated alterations in sphingolipid composition of the umbilical cord artery.

    abstract:OBJECTIVES:Preeclampsia, the most common pregnancy-associated pathological syndrome, is accompanied by significant remodelling of the extracellular matrix and alteration in lipid composition of the umbilical cord artery (UCA). DESIGN AND METHODS:We evaluate the sphingolipid composition of UCA and its alteration in pre...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2009.07.011

    authors: Romanowicz L,Bańkowski E

    更新日期:2009-11-01 00:00:00

  • Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension.

    abstract:OBJECTIVES:The present study was designed to (a) evaluate and compare plasma ammonia levels (PAL) in patients with acute liver failure (ALF) and chronic liver disease (CLD) with or without hepatic encephalopathy (HE); (b) correlate the severity of HE with PAL; and (c) correlate PAL with clinical features of raised intr...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2005.04.013

    authors: Kundra A,Jain A,Banga A,Bajaj G,Kar P

    更新日期:2005-08-01 00:00:00

  • Identification of a complex between fibronectin and aggrecan G3 domain in synovial fluid of patients with painful meniscal pathology.

    abstract:OBJECTIVES:We previously described a panel of four cytokines biomarkers in knee synovial fluid for acute knee pain associated with meniscal pathology. The cytokine biomarkers included interferon gamma (IFN-gamma), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein-1 beta (...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2010.04.069

    authors: Scuderi GJ,Woolf N,Dent K,Golish SR,Cuellar JM,Cuellar VG,Yeomans DC,Carragee EJ,Angst MS,Bowser R,Hanna LS

    更新日期:2010-07-01 00:00:00

  • Relation of aging with oxidative protein damage parameters in the rat skeletal muscle.

    abstract:OBJECTIVES:An increase in oxidative stress may contribute to the development of oxidative protein damage in the aging rat skeletal muscle. Our aim was to reveal protein carbonyl (PCO), advanced oxidation protein products (AOPP), a novel marker of oxidative stress, and protein thiol (P-SH) levels as markers of protein o...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/s0009-9120(02)00407-1

    authors: Cakatay U,Telci A,Kayali R,Tekeli F,Akçay T,Sivas A

    更新日期:2003-02-01 00:00:00

  • Effect of dehydroepiandrosterone (DHEA) treatment on oxidative energy metabolism in rat liver and brain mitochondria. A dose-response study.

    abstract:OBJECTIVES:Effects of treatment with dehydroepiandrosterone (DHEA) on oxidative energy metabolism in rat liver and brain mitochondria were examined. DESIGN AND METHODS:Young adult rats were administered DHEA (0.1, 0.2, 1.0 or 2.0 mg/kg body weight) by subcutaneous route for 7 consecutive days. RESULTS:DHEA treatment ...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2006.08.014

    authors: Patel MA,Katyare SS

    更新日期:2007-01-01 00:00:00

  • Osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) levels in malignant and benign pericardial effusions.

    abstract:OBJECTIVES:Osteoprotegerin (OPG) is a regulator of bone and vascular homeostasis and acts as a decoy receptor for proapoptotic TNF-related apoptosis-inducing ligand (TRAIL). DESIGN AND METHODS:We assessed pericardial and serum levels of OPG and TRAIL in pericardial effusions (PE) of malignant (mPE, n=24) or non-malign...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2011.12.003

    authors: Karatolios K,Pankuweit S,Goettsch C,Hofbauer LC,Timmesfeld N,Al-Fakhri N,Maisch B,Schoppet M

    更新日期:2012-02-01 00:00:00

  • Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: Comparisons to traditionally partitioned reference intervals.

    abstract:BACKGROUND:Reference intervals have traditionally been partitioned by age based on statistical significance and physiological relevance. However, analyte concentration does not change abruptly with age, but rather dynamically. In this study, we establish biochemical marker continuous reference intervals for a Canadian ...

    journal_title:Clinical biochemistry

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.clinbiochem.2019.08.010

    authors: Asgari S,Higgins V,McCudden C,Adeli K

    更新日期:2019-11-01 00:00:00

  • Effects of lifestyle modification on oxidized LDL, reactive oxygen species production and endothelial cell viability in patients with coronary artery disease.

    abstract:OBJECTIVES:We evaluated the effects of lifestyle modification (LM) on lipid profile, oxidative stress and serum-stimulated human coronary artery endothelial cell (HCAEC) viability in coronary artery disease (CAD) patients after 6months. DESIGN AND METHODS:Thirty patients with CAD were randomly assigned to LM intervent...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.clinbiochem.2010.04.056

    authors: Srimahachota S,Wunsuwan R,Siritantikorn A,Boonla C,Chaiwongkarjohn S,Tosukhowong P

    更新日期:2010-07-01 00:00:00

  • A pro-inflammatory glycoprotein biomarker is associated with lower bilirubin in metabolic syndrome.

    abstract:OBJECTIVES:Bilirubin exerts anti-oxidative and anti-inflammatory properties which may beneficially influence the development of cardio-metabolic disorders. A nuclear magnetic resonance (NMR) spectroscopy-based glycoprotein biomarker, designated GlycA, whose signal originates from several glycosylated acute-phase protei...

    journal_title:Clinical biochemistry

    pub_type: 杂志文章

    doi:10.1016/j.clinbiochem.2015.06.016

    authors: Dullaart RP,Gruppen EG,Connelly MA,Lefrandt JD

    更新日期:2015-11-01 00:00:00