Determination Of Urea Research Articles

Potentiometric Urea Biosensor Based on a Urease‐Immobilized Polypyrrole

SummaryUrea is one of the metabolic products of protein metabolism. The accurate determination of urea is important in glomerular filtration rate determination, renal function testing, and other biomedical applications. This research presents a simple fabrication of potentiometric urea biosensor based on a urease‐immobilized polypyrrole (PPy). Thin film of PPy doped with hydroquinone monosulfonate (HQS) was electropolymerized on stainless steel supporting electrode. Urease was immobilized onto the PPy film by mean of physical adsorption. X‐ray photoelectron spectroscopy (XPS) was performed to confirm the existence of urease on PPy surface. The PPy film immobilized with urease activity of 200 U/mL showed the sensitivity of 43.4 ± 3.3 mV/pUrea (r2 > 0.99) in the urea concentration ranging from 0.5 to 10 mM (pUrea 2.0–3.3). The response time was less than 60 sec. The urease‐immobilized PPy film offers a great potential in the use of conducting PPy film as an effective transducer to convert physiochemical change into an electronic signal, enhancing in performance of the biosensor.

Comparative Study of Creatinine and Urea in the Case of Well and Poorly Controlled Diabetes

Abstract The glycosylated hemoglobin is useful in monitoring diabetes regardless of its type allowing a retroactive evaluation over a period of 45 days according to the last studies, being a suggestive mirror for the glycemic status. The protein metabolism is evaluated through biochemical determinations of creatinine and urea. The medical practice is interested in how ensuring a good control or a less good control, of diabetes, will generate changes in the case of these biochemical parameters.

Clinical chemistry measurements with commercially available test slides on a smartphone platform: Colorimetric determination of glucose and urea

BackgkroundRapidly increasing healthcare costs in economically advantaged countries are currently unsustainable, while in many developing nations, even 50-year-old technologies are too expensive to implement. New and unconventional technologies are being explored as solutions to this problem. In this study, we examined the use of a smartphone as the detection platform for 2 well-developed, relatively inexpensive, commercially available clinical chemistry assays as a model for rapid and inexpensive clinical diagnostic testing. MethodsAn Apple iPhone 4 camera phone equipped with a color analysis application (ColorAssist) was combined with Vitros® glucose and urea colorimetric assays. Color images of assay slides at various concentrations of glucose or urea were collected with the iPhone 4 and quantitated in three different spectral ranges (red/green/blue or RGB) using the ColorAssist app. When the diffuse reflectance data was converted into absorbance, it was possible to quantitate glucose or blood urea nitrogen (BUN) over their clinically important concentration ranges (30–515mg/dl for glucose or 2–190mg/dl for BUN), with good linearity (R2=0.9994 or 0.9996, respectively [n=5]). ResultsData collected using the iPhone 4 and canine serum samples were in agreement with results from the instrumental “gold standard” (Beckman Coulter AU480 Chemistry System) (R2=0.9966 and slope=1.0001 for glucose; R2=0.9958 and slope=0.9454 for BUN). Glucose determinations of serum samples made using this smartphone method were as accurate as or more accurate than a commercial colorimetric dry slide analyzer (Heska® Element DC Chemistry Analyzer, Loveland, CO) and 2 glucometers: ReliOn® Ultima (Abbott Diabetes Care Inc) and Presto® (AgaMatrix Inc.H). BUN determinations made using the smartphone approach were comparable in accuracy to the Heska instrument. ConclusionThis demonstration shows that smartphones have the potential to be used as simple, effective colorimetric detectors for quantitative diagnostic tests, and may be applicable for both point-of-care applications in the developed world and field deployment in developing nations.

Potentiometric Biosensor System Based on Recombinant Urease and Creatinine Deiminase for Urea and Creatinine Determination in Blood Dialysate and Serum

AbstractA biosensor system for simultaneous determination of creatinine and urea in blood serum and dialysate samples was developed. It consisted of creatinine and urea biosensors based on a potentiometric transducers with two identical pH‐sensitive field‐effect transistors. In creatinine biosensor, creatinine deiminase immobilized via photopolymerization in PVA/SbQ polymer on one transistor served as a biorecognition element, while bovine serum albumin in PVA/SbQ polymer placed on the second transistor was used for reference. The urea biosensor was created in the same way but recombinant urease was used instead of creatinine deiminase. The linear ranges of creatinine and urea measurement were 0.02–2 mM and 0.5–15 mM, correspondingly, which allowed simultaneous determination of the metabolites. Response time of the biosensor system was 2–3 min; RSD of responses did not exceeded 5 %. The biosensors demonstrated absence of non‐selective response towards components of blood dialysate and serum. Urea and creatinine concentrations were determined in 20 samples of blood dialysate and serum. The results correlated well with traditional methods of analysis. Creatinine and urea biosensors were stable during five months of storage (during this time the responses decreased by about 10 %). The proposed biosensor system can be effectively used for analysis of serum samples and for hemodialysis control.

Determination of neonicotinoid insecticides and their metabolites in honey bee and honey by liquid chromatography tandem mass spectrometry.

The original analytical method for the simultaneous determination and confirmation of neonicotinoids insecticides (imidacloprid, clothianidin, acetamiprid, thiametoxam, thiacloprid, nitenpyram, dinotefuran) and some of their metabolites (imidacloprid guanidine, imidacloprid olefin, imidacloprid urea, desnitro-imidacloprid hydrochloride, thiacloprid-amid and acetamiprid-N-desmethyl) in honey bee and honey was developed. Preparation of honey bee samples involves the extraction with mixture of acetonitrile and ethyl acetate followed by cleaned up using the Sep-Pak Alumina N Plus Long cartridges. Honey samples were dissolved in 1% mixture of acetonitrile and ethyl acetate with addition of TEA, then extracts were cleaned up with Strata X-CW cartridges. The identity of analytes was confirmed using liquid chromatography tandem mass spectrometry. All compounds were separated on a Luna C18 column with gradient elution. The whole procedure was validated according to the requirements of SANCO 12571/2013. The average recoveries of the analytes ranged from 85.3% to 112.0%, repeatabilities were in the range of 2.8-11.2%, within-laboratory reproducibility was in the range of 3.3-14.6%, the limits of quantitation were in the range of 0.1-0.5μgkg(-1), depending of analyte and matrices. The validated method was successfully applied for the determination of clothianidin, imidacloprid and imidacloprid urea in real incurred honey bee samples and clothianidin in honey.

Highly sensitive enzymatic determination of urea based on the pH-dependence of the fluorescence of graphene quantum dots

We report on a nanoparticle-based fluorescent sensing scheme for urea. It is based on the finding that graphene quantum dots (GQDs) display pH-sensitive green fluorescence if photoexcited at 460 nm. Fluorescence is gradually quenched due to an increase in the local pH value as a result of the hydrolysis of urea as catalyzed by urease. The effect was used to quantify urea in the 0.1–100 mM concentration range, with a limit of detection of 0.01 mM. The method was successfully applied to the determination of urea in human serum samples. The method is simple, effective, and therefore holds promise as a platform for sensing urea in blood.

STUDY ON RENAL CHANGES AFTER GENERAL ANESTHESIA WITH SEVOFLURANE, LOW FLOW

INTRODUCTION. Proteinuria is the most common laboratory manifestation of renal disease; in the absence of clinical symptoms, it consists of a urinary excretion of more than 150 mg/day of protein. Glomerular membrane damage, decreased tubular reabsorption or destruction of kidney tissue causes proteinuria. The presence of increased amounts of protein in the urine can be an important indicator of kidney dysfunction. Among the side effects of Sevoflurane, is mentioned the glomerular toxicity effect, as a result of the contact of Sevoflurane with CO2 absorbents, that give rise to toxic compounds: Compound A, B, C, D. Experience in repeated exposure to Sevoflurane is little known, which is why the use of Sevoflurane in patients with renal disease, diabetes and hypertension is not restrictive. In this study we aimed to analyze changes in serum urea and creatinine, post anesthesia in relation to glomerular permeability modification for proteins. MATERIAL AND METHOD. We performed medium and long-term anesthesia, with low flow (2l / min) Sevoflurane, to a total of 155 patients of the Department of Anesthesiology, from the Mures County Hospital in the period 01.10.2009-01.11.2014. We collected demographic data, biological samples of serum and urine preoperatively, 24 and 72 hours postoperatively RESULTS By applying statistical analysis tests Graph Pad Prisma 6 for repetitive data from the 3 intervals, we get the following results: For serum creatinine by Anova table operatively to 24 and 72 hours postoperatively, we obtained a value P = 0.054 by Bartlett test, and a P ’ s testa P = 0.0037 value . Through statistical analysis of blood glucose, preanesthetic, postanesthesia 24 and 72 hours, we obtained the following statistics: by Anova table a P value CONCLUSIONS Determination of serum creatinine and urea, is inadequate for monitoring renal injury produced by A compound. Analyzing the partial and final data of this study, we observed a significant presence of proteins and carbohydrates in urine after surgery, with a maximum at 24 hours and postanesthesia regression trend for 72 hours, but without return to initial values, pre-anesthetic. Maintaining high levels of protein and carbohydrates in urine, at 72 hours in patients with Sepsis, Diabetes, is an important sign, which highlights once again the undesirable effect that Sevoflurane has on kidney Keywords: sevoflurane, proteinuria, creatinine, serum urea. Normal 0 21 false false false RO X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Times New Roman; mso-bidi-theme-font:minor-bidi; mso-fareast-language:EN-US;}

Fluorescein-5-isothiocyanate-conjugated protein-directed synthesis of gold nanoclusters for fluorescent ratiometric sensing of an enzyme-substrate system.

This study describes the synthesis of a dual emission probe for the fluorescent ratiometric sensing of hydrogen peroxide (H2O2), enzyme activity, and environmental pH change. Green-emitting fluorescein-5-isothiocyanate (FITC) was conjugated to the amino groups of bovine serum albumin (BSA). This FITC-conjugated BSA acted as a template for the synthesis of red-emitting gold nanoclusters (AuNCs) under alkaline conditions. Under single wavelength excitation, FITC/BSA-stabilized AuNCs (FITC/BSA-AuNCs) emitted fluorescence at 525 and 670nm, which are sensitive to changes in solution pH and H2O2 concentration, respectively. The effective fluorescence quenching of AuNCs by H2O2 enabled FITC/BSA-AuNCs to ratiometrically detect the H2O2 product-related enzyme system and its inhibition, including glucose oxidase-catalyzed oxidation of glucose, acetylcholinesterase/choline oxidase-mediated hydrolysis and oxidation of acetylcholine, and paraoxon-induced inhibition of acetylcholinesterase activity. When pH-insensitive AuNCs were used as an internal standard, FITC/BSA-AuNCs offered a sensitive and reversible ratiometric sensing of a 0.1-pH unit change in the pH range 5.0-8.5. The pH-induced change in FITC fluorescence enabled FITC/BSA-AuNCs to detect an ammonia product-related enzyme system. This was exemplified with the determination of urea in plasma by urease-mediated hydrolysis of urea.

Kinetic-spectrophotometric determination of neomycin

A new kinetically-based spectrophotometric method for the determination of micro quantities of neomycin is described in this paper. It is an adaptation of the modified Berthelot method which is a widely used colorimetric procedure for urea determination. The method was developed due to neomycin effect on 2,2′-dicarboxyindophenol formation. The experimental conditions for successful determination of neomycin were optimized. The relative standard deviation (RSD) for the neomycin concentration interval of 77–154 μg/mL, ranges from 0.7 to 1%. The method was directly applied to determining neomycin in ophthalmic drops. The obtained results in analyzed pharmaceutical samples were in accordance with disc-diffusion microbiological method results.

Potentiometric biosensor for determination of urea in milk using immobilized Arthrobacter creatinolyticus urease.

The extracellular urease from Arthrobacter creatinolyticus was partially purified by ammonium sulfate precipitation and immobilized on PAN [poly(acrylonitrile-methylmethacrylate-sodium vinylsulfonate)] membrane. The urease immobilized PAN membrane exhibited an activity of 97.92U/cm(2) under the optimum conditions of 1.0% enzyme concentration, 15% glutaraldehyde, 24h immobilization time and temperature of 4°C. The changes in surface morphology of the membrane after immobilization were studied by SEM and ATR-FTIR analysis. Immobilized membrane was associated with potentiometric electrode for calibration of biosensor and the results showed a linear response for wide range of urea concentration from 1 to 100mM. The immobilized urease had good storage stability for a period of 70days at 4°C and could be effectively reused for 13cycles. Urease immobilized membrane was also employed in analysis of urea spiked milk samples.

Determination of urea in canned foods by high performance liquid chromatography-fluorescence detection coupled with precolumn derivatization

A method for the determination of urea residue in canned foods by high performance liquid chromatography-fluorescence detection (HPLC-FLD) coupled with precolumn derivatization was established. The sample (5.0 g), including canned edible fungi, fruit, vegetable, fish, and meat was extracted with 20 mL 1% (v/v) acetic acid solution. The extract was centrifuged, filtrated, and then derivatized with xanthydrol. The analysis was completed with HPLC-FLD. A good linear relationship was obtained in the range of 0.1-500 mg/L with the correlation coefficients more than 0.9995. The average recoveries of urea spiked at 0.001-30 g/kg levels in five kinds of canned foods ranged from 80.2% to 109.7% with the RSDs of 2.05%-6.53%. The limit of detection (LOD) was 0.5 mg/kg, and the limit of quantitation (LOQ) was 1.0 mg/kg. The proposed procedure was then applied to the analysis of 168 real samples collected from Xiamen, Fujian Province, China. The existence of urea was found in three pork cans with contents of 10.6, 62.1 and 2.6 mg/kg, respectively. The method is stable, reliable, simple and suitable for the determination of urea in canned foods, and has great potential for routine analysis in foodstuffs.

Enzyme biosensor systems based on porous silicon photoluminescence for detection of glucose, urea and heavy metals

A phenomenon of changes in photoluminescence of porous silicon at variations in medium pH is proposed to be used as a basis for the biosensor system development. The method of conversion of a biochemical signal into an optical one is applied for direct determination of glucose and urea as well as for inhibitory analysis of heavy metal ions. Changes in the quantum yield of porous silicon photoluminescence occur at varying pH of the tested solution due to the enzyme–substrate reaction. When creating the biosensor systems, the enzymes urease and glucose oxidase (GOD) were used as a bioselective material; their optimal concentrations were experimentally determined. It was shown that the photoluminescence intensity of porous silicon increased by 1.7 times when increasing glucose concentration in the GOD-containing reaction medium from 0 to 3.0mM, and decreased by 1.45 times at the same increase in the urea concentration in the urease-containing reaction medium. The calibration curves of dependence of the biosensor system responses on the substrate concentrations are presented. It is shown that the presence of heavy metal ions (Cu2+, Pb2+, and Cd2+) in the tested solution causes an inhibition of the enzymatic reactions catalyzed by glucose oxidase and urease, which results in a restoration of the photoluminescence quantum yield of porous silicon. It is proposed to use this effect for the inhibitory analysis of heavy metal ions.

Urea impedimetric biosensor based on reactive RF magnetron sputtered zinc oxide nanoporous transducer

Uniform sputtered nanoporous zinc oxide (Nano-ZnO) thin film on the conductive fluorinated-tin oxide (FTO) layer was applied to immobilize urease enzyme (Urs) for urea detection. Highly uniform nanoporous ZnO thin film were obtained by reactive radio frequency (RF) magnetron sputtering system at the optimized instrumental deposition conditions. Characterization of the surface morphology and roughness of ZnO thin film by field emission-scanning electron microscopy (FE-SEM) exhibits cavities of nanoporous film as an effective biosensing area for enzyme immobilization. Step by step monitoring of FTO/Nano-ZnO/Urs biosensor fabrication were performed using electrochemical methods such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Fabricated FTO/Nano-ZnO/Urs biosensor was used for urea determination using EIS experiments. The impedimetric results show high sensitivity for urea detection within 0.83–23.24mM and limit of detection as 0.40mM.

Hemolymph parameters as physiological biomarkers in American lobster (Homarus americanus) for monitoring the effects of two commercial maintenance methods

Live lobsters are considered a fish product by European laws but no invertebrates welfare reference exists in European legislation. In this work the effect of commercial storage stress considering two different commercial maintenance methods (air exposure vs seawater resubmission) were evaluated. Thirteen different physiological variables of the hemolymph were analyzed: glucose, lactate, total protein, cholesterol, triglycerides, ammonia, chloride, calcium, magnesium, sodium, potassium and urea concentration, total haemocyte counts. Bacteriological analysis of hemolymph was performed in order to determine the possible penetration of microorganisms in the tissues. In this work, for the first time, the urea concentration was determined in these species: at arrival this parameter in hemolymph was 2.74±1.04mgdl−1, after 12h in seawater the urea level decreased to 1.17±0.72mgdl−1. Thanks to this study, a single global parameter useful to measure the distress status was not evidenced, even if the determination of protein concentration was the easiest and cheapest one, although influenced by several factors. Ammonia and urea determination were the most specific parameters for the determination of the air transport distress.

Determination of urea and creatinine by chronoamperometry

Methods are developed for the non-enzymatic chronoamperometric determination of urea in blood serum and creatinine in model solutions imitating the composition of blood serum. The selectivity of determination is ensured using columns packed with an anion-exchange resin for urea or synthesized molecularly imprinted polymers for creatinine.

Application of potentiometric biosensor based on recombinant urease for urea determination in blood serum and hemodialyzate

Potentiometric biosensor based on two identical pH-sensitive field-effect transistors for urea determination was developed. Recombinant urease with low affinity to urea (Km=200mM) was immobilized via entrapment in PVA/SbQ photopolymer on one transistor and served as a biorecognition element of the biosensor, while bovine serum albumin in PVA/SbQ photopolymer placed on the second transistor was used for reference. Biosensor was characterized by a wide range of urea determination: 0.5–15mM linear range (operational detection range – 0.5–40mM) and quick response time (1–2min). Samples of blood serum and hemodialysate without urea caused no biosensor response. All this allowed analysis of blood serum samples that were diluted 10 times, what led to smaller measurement error in comparison with 100–500 times dilution in case of biosensors based on non-modified urease from soy beans. Urea concentrations in 10 samples of serum were determined; biosensor results correlated well with two control methods of urea measurement. Furthermore, kinetics of decreasing urea concentration in dialysate during hemodialysis was demonstrated. Biosensor measurements of dialysate samples were verified by traditional colorimetric determination of urea. Proposed biosensor can be effectively used for analysis of samples with different concentrations of urea and for hemodialysis control. What is more, characteristics of the biosensor make possible real-time measurements of urea concentration during hemodialysis by pumping dialysis fluid through the working cell. Biosensor showed no significant decrease of responses during 5 month of storage.

Efectos adversos de la aplicación ambulatoria de inmunoglobulina intravenosa en adultos con inmunodeficiencia común variable

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, affecting 1:25,000-75,000 people. It is characterized by the absence or decrease antibody production. Treatment for CVID consists on human immunoglobulin administration, and the intravenous route is the most common route for administration, at 400-800 mg/kg of weight every 3-4 weeks. Adverse effects associated with intravenous immunoglobulin (IVIg) use occur in 25% of all infusions, with severe adverse reactions presenting in less than 1% of all patients. Acute renal failure can occur as a severe adverse reaction, which presents 1-10 days after starting IVIg treatment. In our center we implemented an ambulatory scheme for IVIg administration, which allows its administration in an average of 3 hours, without severe adverse effects. To describe adverse effects and to evaluate the frequency of renal failure secondary to ambulatory IVIg administration in patients with common variable immunodeficiency. A descriptive and prospective study was done including adult patients con definitive diagnosis of common variable immunodeficiency, receiving IVIg at replacement dose every 3 weeks. All patients were evaluated with clinical exploration, somatometry, serum creatinine, albumin and urea determination, 24 hours creatinine clearance, glomerular filtration rate with CKD-EPI, and immediate renal function associated with accumulated IVIg. Results were analyzed with descriptive statistics. We determined adverse effects in 25 patients with common variable immunodeficiency (15 women and 10 men, average age 36.7 years), during a 10 months period (January-September 2013). During this period 284 IVIg infusions were administered using our scheme, frequency of adverse effects were 12.9%, with 5.2% of early adverse effects and 7.7% late adverse effects, all being mild to moderate, in some cases required analgesic and/or antihistamine administration, without having to stop the IVIg infusion. In the renal function study 19 patients were included (12 women and 7 men, average age 36 years, average weigh 58.74 kg and average height 1.60 m), evaluated from January 2009 to October 2013. Average serum creatinine was 0.76 ± 0.18 mg/dL, average serum urea was 28.6 ± 7.6 mg/dL, none patient presenting acute renal failure. Glomerular filtration rate was determined with CKD-EPI formula, and the average was 116 ± 34 mL/min/1.73 m2, finding chronic renal failure in 4 patients. Average 24 hours creatinine clearance was 98.64 ± 22 mL/min/1.73 m2, with chronic renal failure data in 6 patients. There were no severe adverse effects with this ambulatory IVIg scheme (anaphylaxis, acute renal failure). We did not find data of acute renal failure secondary to IVIg administration in this population, but we did find data of chronic renal failure secondary to IVIg administration through 24 hours creatinine clearance in 6 patients. No relation was found between accumulated IVIg dose in the last 5 years and decreased glomerular filtration rate. Another benefit worth of mentioning with this scheme is the reduction in costs for the health institution and to the patient.

Simultaneous determination of glucose, triglycerides, urea, cholesterol, albumin and total protein in human plasma by Fourier transform infrared spectroscopy: Direct clinical biochemistry without reagents

ObjectiveDirect measurement of chemical constituents in complex biologic matrices without the use of analyte specific reagents could be a step forward toward the simplification of clinical biochemistry. Problems related to reagents such as production errors, improper handling, and lot-to-lot variations would be eliminated as well as errors occurring during assay execution.We describe and validate a reagent free method for direct measurement of six analytes in human plasma based on Fourier-transform infrared spectroscopy (FTIR). Design and methodsBlood plasma is analyzed without any sample preparation. FTIR spectrum of the raw plasma is recorded in a sampling cuvette specially designed for measurement of aqueous solutions. For each analyte, a mathematical calibration process is performed by a stepwise selection of wavelengths giving the optimal least-squares correlation between the measured FTIR signal and the analyte concentration measured by conventional clinical reference methods. The developed calibration algorithms are subsequently evaluated for their capability to predict the concentration of the six analytes in blinded patient samples. ResultsThe correlation between the six FTIR methods and corresponding reference methods were 0.87<R2<1.00. The interassay imprecision meets international quality criteria for all the six analytes. The linearity of the FTIR methods extends over the clinically significant concentration ranges. Visible hemolysis and icterus have some influence on the measurements. Plasma samples can be stored at 2–8°C for at least 8days before the analysis. ConclusionsThe developed FTIR methods use a simple and robust technology to achieve stable and accurate results that meet international quality criteria for the measurement of glucose, triglycerides, urea, cholesterol, albumin and total protein in human plasma.

Application of enzyme/zeolite sensor for urea analysis in serum

Urea biosensor based on zeolite-adsorbed urease was applied for analysis of blood serum samples. It should be noted, that this biosensor has a number of advantages, such as simple and fast performance, the absence of toxic compounds during biosensor preparation, high reproducibility and repeatability (RSD=9% and 4%, respectively). The linear range of urea determination by using the biosensor was 0.003–0.75mM, and the limit of urea detection was 3μM. The method of standard addition was used for analysis of serum samples with 500-fold dilution. Total time of analysis was 10min. Good reproducibility of urea determination in real samples was demonstrated (RSD=10%). Biosensor results were verified by using a common method of urea determination (diacetyl monoxime reaction). It was shown that by using this biosensor distinguishing healthy people from people with renal dysfunction becomes easier.

The role of 3 external quality assessment programs in assessment of analytical quality on determination of serum creatinine and urea

Objective To describe and compare the roles of 3 external quality assessment programs in assessment of analytical quality of serum creatinine and urea. Methods Research in quality management methods.Sixty-five laboratories those enrolled in the Natonal Center for Clinical Laboratories′ programs of routine chemistry external quality assessment (EQA), trueness verification (TV) for small molecular metabolites and external comparison of internal quality control (IQC) simultaneously in 2013 were selected，the performances of those laboratories of serum creatinine (crea) and urea in terms of total errors(TE), bias and CV were obtained by using the above 3 programs, and these performance were assessed against the criterion listed in the analytical quality specifications for routine analysis in clinical biochemistry (WS/T 403-2012). The failure ratio of 65 laboratories on each performance was calculated, the sensitivity of 3 external quality assessment programs in detection of analytical quality deficiency among clinical laboratories were compared. Results Only 1 laboratory failed in the 1st routine chemistry EQA in terms of TE of creatinine, failure ratio is 1.5%(1/65). Three laboratories failed in the 2nd EQA and caused a failure ratio of 4.6%(3/65). For serum urea, 3 laboratories failed in the 1st routine chemistry EQA with a failure ratio of 4.6%(3/65). Two laboratories failed in the 2nd EQA with a failure ratio of 3.1%(2/65).The failure ratios of creatinine determination in two samples in TV were 41.5%(24/65) and 21.5%(14/65) respectively, and the failure ratio of urea determination were 53.8%(36/65) and 32.3%(21/65) respectively. In the program of external comparison of IQC，the CVs of creatinine and urea determination ranged from 0.7% to 6.2% and from 1.0% to 7.2% respectively, their respective failure ratio range were 15.4%(10/65) and 40.0%(26/65). The failure ratio in routine EQA were much less than those in the other two programs, the laboratories failed in routine EQA program were all failed in trueness verification or/and the comparison of IQC programs, but not vice versa. Conclusions By participating in the programs of routine EQA, TV and comparison of IQC laboratories could assess the performances of inaccuracy, bias and imprecision. Laboratories should participate in different external quality assurance programs to detect their quality issues and get improved.（Chin J Lab Med,2014,37:357-361） Key words: Laboratories, hospital; Quality control; Creatinine; Urea; Uncertainty