0003183807190c501V9.

UA2
Uric Acid ver.2
Order information
Analyzer(s) on which cobas c pack(s) can be used
03183807 190 Uric Acid ver.2 400 tests System‑ID 07 6615 1 Roche/Hitachi cobas c 311, cobas c 501/502
10759350 190 Calibrator f.a.s. (12 x 3 mL) Code 401
10759350 360 Calibrator f.a.s. (12 x 3 mL, for USA) Code 401
12149435 122 Precinorm U plus (10 x 3 mL) Code 300
12149435 160 Precinorm U plus (10 x 3 mL, for USA) Code 300
12149443 122 Precipath U plus (10 x 3 mL) Code 301
12149443 160 Precipath U plus (10 x 3 mL, for USA) Code 301
10171743 122 Precinorm U (20 x 5 mL) Code 300
10171735 122 Precinorm U (4 x 5 mL) Code 300
10171778 122 Precipath U (20 x 5 mL) Code 301
10171760 122 Precipath U (4 x 5 mL) Code 301
05117003 190 PreciControl ClinChem Multi 1 (20 x 5 mL) Code 391
05947626 190 PreciControl ClinChem Multi 1 (4 x 5 mL) Code 391
05947626 160 PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) Code 391
05117216 190 PreciControl ClinChem Multi 2 (20 x 5 mL) Code 392
05947774 190 PreciControl ClinChem Multi 2 (4 x 5 mL) Code 392
05947774 160 PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) Code 392
04489357 190 Diluent NaCl 9 % (50 mL) System‑ID 07 6869 3

English 4‑aminophenazone to form a quinone‑diimine dye. The intensity of the red

color formed is proportional to the uric acid concentration and is determined
System information photometrically.
For cobas c 311 analyzer:
Test principle
UA2: ACN 700 (serum/plasma)
Enzymatic colorimetric test.
UA2‑U: ACN 702 (urine)
Uricase cleaves uric acid to form allantoin and hydrogen peroxide.
For cobas c 501 analyzer:
UA2: ACN 700 (serum/plasma/urine) Uricase
For cobas c 502 analyzer: Uric acid + 2 H2O + O2 allantoin + CO2 + H2O2
UA2: ACN 8700 (serum/plasma) In the presence of peroxidase, 4‑aminophenazone is oxidized by hydrogen
UA2‑U: ACN 8702 (urine) peroxide to a quinone‑diimine dye.
Intended use Peroxidase
In vitro test for the quantitative determination of uric acid in human serum,
plasma and urine on Roche/Hitachi cobas c systems. 2 H2O2 + H+ + TOOSa quinone‑diimine
+ 4‑aminophenazone dye + 4 H2O
Summary1,2,3,4,5,6,7,8,9,10,11,12,13,14
Uric acid is the final product of purine metabolism in the human organism. The color intensity of the quinone‑diimine formed is directly proportional to
Uric acid measurements are used in the diagnosis and treatment of the uric acid concentration and is determined by measuring the increase in
numerous renal and metabolic disorders, including renal failure, gout, absorbance.
leukemia, psoriasis, starvation or other wasting conditions, and of patients a) N‑ethyl‑N‑(2‑hydroxy‑3‑sulfopropyl)‑3‑methylaniline
receiving cytotoxic drugs.
Reagents - working solutions
The oxidation of uric acid provides the basis for two approaches to the
quantitative determination of this purine metabolite. One approach is the R1 Phosphate buffer: 0.05 mol/L, pH 7.8; TOOS: 7 mmol/L; fatty
reduction of phosphotungstic acid in an alkaline solution to tungsten blue, alcohol polyglycol ether: 4.8 %; ascorbate oxidase (EC 1.10.3.3;
which is measured photometrically. The method is, however, subject to
interferences from drugs and reducing substances other than uric acid. zucchini) ≥ 83.5 µkat/L (25 °C); stabilizers
A second approach, described by Praetorius and Poulsen, utilizes the R3 Phosphate buffer: 0.1 mol/L, pH 7.8; potassium
enzyme uricase to oxidize uric acid; this method eliminates the hexacyanoferrate (II): 0.3 mmol/L; 4‑aminophenazone ≥ 3 mmol/L;
interferences intrinsic to chemical oxidation. Uricase can be employed in
methods that involve the UV measurement of the consumption of uric acid uricase (EC 1.7.3.3; Arthrobacter protophormiae) ≥ 83.4 µkat/L
or in combination with other enzymes to provide a colorimetric assay. (25 °C); peroxidase (POD) (EC 1.11.1.7; horseradish) ≥ 50 µkat/L
Another method is the colorimetric method developed by Town et al. The (25 °C); stabilizers
sample is initially incubated with a reagent mixture containing ascorbate R1 is in position B and R3 is in position C.
oxidase and a clearing system. In this test system it is important that any
ascorbic acid present in the sample is eliminated in the preliminary reaction; Precautions and warnings
this precludes any ascorbic acid interference with the subsequent POD For in vitro diagnostic use.
indicator reaction. Upon addition of the starter reagent, oxidation of uric acid Exercise the normal precautions required for handling all laboratory
by uricase begins. reagents.
The Roche assay described here is a slight modification of the colorimetric Disposal of all waste material should be in accordance with local guidelines.
method described above. In this reaction, the peroxide reacts in the Safety data sheet available for professional user on request.
presence of peroxidase (POD), For USA: For prescription use only.
N‑ethyl‑N‑(2‑hydroxy‑3‑sulfopropyl)‑3‑methylaniline (TOOS), and

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UA2
Uric Acid ver.2

This kit contains components classified as follows in accordance with the Materials provided
Regulation (EC) No. 1272/2008: See “Reagents – working solutions” section for reagents.
Materials required (but not provided)
See “Order information” section
General laboratory equipment
Assay
Danger For optimum performance of the assay follow the directions given in this
document for the analyzer concerned. Refer to the appropriate operator’s
H318 Causes serious eye damage. manual for analyzer‑specific assay instructions.
Prevention: The performance of applications not validated by Roche is not warranted
and must be defined by the user.
P280 Wear eye protection/ face protection.
Application for serum and plasma
Response:
cobas c 311 test definition
P305 + P351 IF IN EYES: Rinse cautiously with water for several
Assay type 2‑Point End
+ P338 + minutes. Remove contact lenses, if present and easy to do.
P310 Continue rinsing. Immediately call a POISON CENTER or Reaction time / Assay points 10 / 23‑27
doctor/ physician. Wavelength (sub/main) 700/546 nm
Product safety labeling primarily follows EU GHS guidance. Reaction direction Increase
Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336 Units mg/dL (µmol/L, mg/L)
Reagent handling Reagent pipetting Diluent (H2O)
Ready for use
R1 72 µL 25 µL
Storage and stability
R3 14 µL 20 µL
UA2 Sample volumes Sample Sample dilution
Shelf life at 2‑8 °C: See expiration date on Sample Diluent
cobas c pack label. (NaCl)
On‑board in use and refrigerated on the 8 weeks Normal 3 µL – –
analyzer:
Decreased 12 µL 15 µL 135 µL
Increased 3 µL – –
NaCl Diluent 9 %
Shelf life at 2‑8 °C: See expiration date on cobas c 501 test definition
cobas c pack label. Assay type 2‑Point End
On‑board in use and refrigerated on the 12 weeks Reaction time / Assay points 10 / 34‑42
analyzer: Wavelength (sub/main) 700/546 nm
Specimen collection and preparation Reaction direction Increase
For specimen collection and preparation only use suitable tubes or
collection containers. Units mg/dL (µmol/L, mg/L)
Only the specimens listed below were tested and found acceptable. Reagent pipetting Diluent (H2O)
Serum. R1 72 µL 25 µL
Plasma: Li‑heparin and K2‑EDTA plasma.
EDTA plasma values are approximately 7 % lower than serum values. R3 14 µL 20 µL
The sample types listed were tested with a selection of sample collection Sample volumes Sample Sample dilution
tubes that were commercially available at the time of testing, i.e. not all Sample Diluent
available tubes of all manufacturers were tested. Sample collection systems (NaCl)
from various manufacturers may contain differing materials which could
affect the test results in some cases. When processing samples in primary Normal 3 µL – –
tubes (sample collection systems), follow the instructions of the tube
manufacturer. Decreased 12 µL 15 µL 135 µL
Urine: Assay urinary uric acid as soon as possible. Do not refrigerate. Increased 3 µL – –
To prevent ureate precipitation in urine samples, add sodium hydroxide to
keep urine alkaline (pH > 8.0). To achieve stated uric acid stability, add cobas c 502 test definition
NaOH prior to sample collection. Urine samples are diluted 1 + 10 with Assay type 2‑Point End
distilled/deionized water or 0.9 % NaCl. This dilution is taken into account in
the calculation of the results. Reaction time / Assay points 10 / 34‑42
Centrifuge samples containing precipitates before performing the assay. Wavelength (sub/main) 700/546 nm
Stability in serum/plasma:15 5 days at 2‑8 °C Reaction direction Increase
6 months at (-15)‑(-25) °C Units mg/dL (µmol/L, mg/L)
Stability in urine16 (upon 4 days at 15‑25 °C Reagent pipetting Diluent (H2O)
NaOH addition): R1 72 µL 25 µL
R3 14 µL 20 µL

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Uric Acid ver.2

Sample volumes Sample Sample dilution Normal 3 µL 15 µL 150 µL

Sample Diluent Decreased 3 µL 6 µL 160 µL
(NaCl) Increased 6 µL 15 µL 150 µL
Normal 3 µL – –
Calibration
Decreased 12 µL 15 µL 135 µL
Calibrators S1: H2O
Increased 6 µL – –
S2: C.f.a.s.
Application for urine
Calibration mode Linear
cobas c 311 test definition
Calibration frequency 2‑point calibration
Assay type 2‑Point End
- after reagent lot change
Reaction time / Assay points 10 / 23‑27
- as required following quality control
Wavelength (sub/main) 700/546 nm procedures
Reaction direction Increase Traceability: This method has been standardized against ID/MS.17
Units mg/dL (µmol/L, mg/L) Quality control
Reagent pipetting Diluent (H2O) Serum/plasma
R1 72 µL 25 µL For quality control, use control materials as listed in the “Order information”
section. In addition, other suitable control material can be used.
R3 14 µL 20 µL
Urine
Sample volumes Sample Sample dilution Quantitative urine controls are recommended for routine quality control.
Sample Diluent The control intervals and limits should be adapted to each laboratory’s
(NaCl) individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be taken if
Normal 3 µL 15 µL 150 µL values fall outside the defined limits.
Decreased 3 µL 6 µL 160 µL Follow the applicable government regulations and local guidelines for
Increased 3 µL 15 µL 150 µL quality control.
Calculation
cobas c 501 test definition Roche/Hitachi cobas c systems automatically calculate the analyte
Assay type 2‑Point End concentration of each sample.
Reaction time / Assay points 10 / 34‑42 Conversion factors: mg/dL x 59.5 = µmol/L
Wavelength (sub/main) 700/546 nm mg/dL x 10 = mg/L
Reaction direction Increase Limitations - interference
Units mg/dL (µmol/L, mg/L) Criterion: Recovery within ± 10 % of initial value at an uric acid
Reagent pipetting Diluent (H2O) concentration of 7 mg/dL (417 µmol/L).
Serum/plasma
R1 72 µL 25 µL
Icterus:18 No significant interference up to an I index of 40 for conjugated
R3 14 µL 20 µL and unconjugated bilirubin (approximate conjugated and unconjugated
Sample volumes Sample Sample dilution bilirubin concentration: 684 µmol/L or 40 mg/dL).
Hemolysis:18 No significant interference up to an H index of 1000
Sample Diluent (approximate hemoglobin concentration: 621 µmol/L or 1000 mg/dL).
(NaCl) Lipemia (Intralipid):18 No significant interference up to an L index of 1500.
Normal 3 µL 15 µL 150 µL There is poor correlation between the L index (corresponds to turbidity) and
triglycerides concentration.
Decreased 3 µL 6 µL 160 µL
Ascorbic acid < 0.17 mmol/L (< 3 mg/dL) does not interfere.
Increased 3 µL 15 µL 150 µL Drugs: No interference was found at therapeutic concentrations using
common drug panels.19,20 Exceptions: Calcium dobesilate causes artificially
cobas c 502 test definition low uric acid results.
Assay type 2‑Point End Uricase reacts specifically with uric acid. Other purine derivatives can inhibit
Reaction time / Assay points 10 / 34‑42 the uric acid reaction.
Dicynone (Etamsylate) at therapeutic concentrations may lead to false‑low
Wavelength (sub/main) 700/546 nm results.
Reaction direction Increase In very rare cases, gammopathy, in particular type IgM (Waldenström’s
Units mg/dL (µmol/L, mg/L) macroglobulinemia), may cause unreliable results.21
Urine
Reagent pipetting Diluent (H2O)
Drugs: No interference was found at therapeutic concentrations using
R1 72 µL 25 µL common drug panels.20 Exceptions: Calcium dobesilate, Levodopa and
R3 14 µL 20 µL methyldopa can all cause artificially low uric acid results.
High homogentisic acid concentrations in urine samples lead to false
Sample volumes Sample Sample dilution results.
Sample Diluent Dicynone (Etamsylate) at therapeutic concentrations may lead to false‑low
(NaCl) results.

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Uric Acid ver.2

For diagnostic purposes, the results should always be assessed in Specific performance data
conjunction with the patient’s medical history, clinical examination and other Representative performance data on the analyzers are given below.
findings. Results obtained in individual laboratories may differ.
ACTION REQUIRED Precision
Special Wash Programming: The use of special wash steps is mandatory
when certain test combinations are run together on Roche/Hitachi Precision was determined using human samples and controls in an internal
cobas c systems. The latest version of the carry‑over evasion list can be protocol with repeatability (n = 21) and intermediate precision (3 aliquots
found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further per run, 1 run per day, 21 days). The following results were obtained:
instructions refer to the operator’s manual. cobas c 502 analyzer: All Serum/plasma
special wash programming necessary for avoiding carry‑over is available
via the cobas link, manual input is not required. Repeatability Mean SD CV
Where required, special wash/carry‑over evasion programming must mg/dL (µmol/L) mg/dL (µmol/L) %
be implemented prior to reporting results with this test.
Precinorm U 4.54 (270) 0.04 (2) 0.9
Limits and ranges
Measuring range Precipath U 11.1 (660) 0.1 (6) 0.7
Serum/plasma Human serum 1 4.03 (240) 0.04 (2) 1.0
0.2‑25.0 mg/dL (11.9‑1487 µmol/L) Human serum 2 7.23 (430) 0.06 (4) 0.8
Determine samples having higher concentrations via the rerun function.
Dilution of samples via the rerun function is a 1:2.5 dilution. Results from Intermediate precision Mean SD CV
samples diluted using the rerun function are automatically multiplied by a mg/dL (µmol/L) mg/dL (µmol/L) %
factor of 2.5.
Urine Precinorm U 4.47 (266) 0.07 (4) 1.5
2.2‑275 mg/dL (131‑16362 µmol/L) Precipath U 11.1 (660) 0.2 (12) 1.6
Determine samples having higher concentrations via the rerun function. Human serum 3 3.96 (236) 0.05 (3) 1.3
Dilution of samples via the rerun function is a 1:2.5 dilution. Results from
samples diluted using the rerun function are automatically multiplied by a Human serum 4 7.17 (427) 0.10 (6) 1.3
factor of 2.5. Urine
Lower limits of measurement
Repeatability Mean SD CV
Lower detection limit of the test
Serum/plasma mg/dL (µmol/L) mg/dL (µmol/L) %
0.2 mg/dL (11.9 µmol/L) Control level 1 11.7 (696) 0.1 (6) 1.2
The lower detection limit represents the lowest measurable analyte level Control level 2 21.7 (1291) 0.3 (18) 1.3
that can be distinguished from zero. It is calculated as the value lying
3 standard deviations above that of the lowest standard (standard 1 + 3 SD, Urine 1 28.8 (1714) 0.6 (36) 2.1
repeatability, n = 21). Urine 2 32.5 (1934) 0.5 (30) 1.5
Urine
2.2 mg/dL (131 µmol/L) Intermediate precision Mean SD CV
The lower detection limit represents the lowest measurable analyte level mg/dL (µmol/L) mg/dL (µmol/L) %
that can be distinguished from zero. It is calculated as the value lying
3 standard deviations above that of the lowest standard (standard 1 + 3 SD, Control level 1 11.4 (678) 0.2 (12) 1.9
repeatability, n = 21). Control level 2 21.3 (1267) 0.3 (18) 1.6
Expected values Urine 3 29.3 (1743) 0.9 (54) 3.0
Serum/plasma22 Urine 4 32.1 (1910) 0.8 (48) 2.3
Males: 3.4‑7.0  mg/dL (202.3‑416.5 µmol/L) Method comparison
Females: 2.4‑5.7 mg/dL (142.8‑339.2 µmol/L) Uric acid values for human serum, plasma and urine obtained on a
Roche/Hitachi cobas c 501 analyzer (y) were compared with those
Urine (reference range according to Krieg and Colombo) determined using the corresponding reagent on a Roche/Hitachi 917
analyzer (x).
1st morning urine23 37‑92 mg/dL (2200‑5475 µmol/L)
Serum/plasma
24‑hour urine24 200‑1000 mg/day (1200‑5900 µmol/day) Sample size (n) = 89
corresponding to 13‑67 mg/dL (773‑3986 µmol/L)
Passing/Bablok25 Linear regression
(calculated from a urine volume of 1.5  L/24 h)
y = 0.993x + 0.158 mg/dL y = 0.986x + 0.224 mg/dL
Urine (reference range according to Tietz)15 τ = 0.969 r = 1.000
Average diet 250‑750 mg/24 hours The sample concentrations were between 2.70 and 23.4 mg/dL (161 and
Low purine diet 1392 µmol/L).
Females < 400 mg/24 hours Urine
Sample size (n) = 86
Males < 480 mg/24  hours
High purine diet < 1000 mg/24 hours Passing/Bablok25 Linear regression
Each laboratory should investigate the transferability of the expected values y = 0.997x + 0.456 mg/dL y = 0.998x + 0.522 mg/dL
to its own patient population and if necessary determine its own reference τ = 0.952 r = 0.999
ranges.

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Uric Acid ver.2

The sample concentrations were between 6.35 and 269 mg/dL (378 and 25 Bablok W, Passing H, Bender R, et al. A general regression procedure
16006 µmol/L). for method transformation. Application of linear regression procedures
for method comparison studies in clinical chemistry, Part III. J Clin
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2 Keller H, ed. Klinisch-chemische Labordiagnostik für die Praxis, 2nd ed. a decimal numeral. Separators for thousands are not used.
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4 Kageyama N. A direct colorimetric determination of uric acid in serum Contents of kit
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FOR US CUSTOMERS ONLY: LIMITED WARRANTY
6 Kaiser E, et al. Wiener Klin Wschr 1972;84:217. Roche Diagnostics warrants that this product will meet the specifications
7 Kim EK, Waddel LD, Sunderland MLE, et al. Observations on stated in the labeling when used in accordance with such labeling and will
Diagnostic Kits for the Determination of Uric Acid. Clin Biochem be free from defects in material and workmanship until the expiration date
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printed on the label. THIS LIMITED WARRANTY IS IN LIEU OF ANY
8 Elking MP, Karat HF. Drug induced modifications of laboratory test OTHER WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED
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WARRANTY OF MERCHANTABILITY OR FITNESS FOR PARTICULAR
9 Young DS, Thomas DW, Friedman RB, et al. Effects of drugs on PURPOSE. IN NO EVENT SHALL ROCHE DIAGNOSTICS BE LIABLE
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10 Küffer H. Causes of misleading laboratory results: disturbances due to DAMAGES.
drugs. Therap Umschau 1971;28(10):669-680.
COBAS, COBAS C, PRECICONTROL, PRECINORM and PRECIPATH are trademarks of Roche.
11 Haug HG. Diagnostik 1972;5:85. All other product names and trademarks are the property of their respective owners.
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13 Praetorius E, Poulsen H. Enzymatic determination of uric acid; with
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14 Town MH, Gehm S, Hammer B, et al. A sensitive colorimetric method www.roche.com
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1985;23:591. Roche Diagnostics, Indianapolis, IN
US Customer Technical Support 1-800-428-2336
15 Wu AHB, ed. Tietz Clinical Guide to Laboratory Tests, 4th edition. St.
Louis (MO): Saunders Elsevier 2006;1098-1100.
16 WHO Publication: Use of anticoagulants in diagnostic laboratory
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17 Siekmann L. Determination of uric acid in human serum by isotope
dilution-mass spectrometry. J Clin Chem Clin Biochem
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18 Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of
Interferences in Clinical Chemistry Instrumentation.
Clin Chem 1986;32:470-475.
19 Breuer J. Report on the Symposium “Drug effects in Clinical Chemistry
Methods”. Eur J Clin Chem Clin Biochem 1996;34:385-386.
20 Sonntag O, Scholer A. Drug interference in clinical chemistry:
recommendation of drugs and their concentrations to be used in drug
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21 Bakker AJ, Mücke M. Gammopathy interference in clinical chemistry
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22 Thefeld W, Hoffmeister H, Busch EW, et al. Normalwerte der
Serumharnsäure in Abhängigkeit von Alter und Geschlecht mit einem
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23 Krieg M, Gunsser KJ, Steinhagen-Thiessen E, et al. Vergleichende
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