8L25-30
LITHIUM
NOTE: This package insert must be read carefully prior to product use.
Package insert instructions must be followed accordingly. Reliability of
assay results cannot be guaranteed if there are any deviations from the
instructions in this package insert.
NOTE: Changes Highlighted
WARNINGS AND PRECAUTIONS
Precautions for Users
• For in vitro diagnostic use.
• Do not use components beyond the expiration date.
• Do not mix materials from different kit lot numbers.
•
Protect reagent from light.
INTENDED USE
The MULTIGENT Lithium assay is intended for the quantitation of lithium
in serum and plasma using the ARCHITECT c Systems.
• This product contains sodium azide; for a specific listing, refer to
the REAGENTS section of this package insert. Contact with acids
liberates very toxic gas. This material and its container must be
disposed of in a safe way.
NOTE: Refer to Section 8 of the ARCHITECT System Operations
Manual for proper handling and disposal of reagents containing
sodium azide.
• CAUTION: This product requires the handling of human specimens.
It is recommended that all human sourced materials be considered
potentially infectious and be handled in accordance with the OSHA
Standard on Bloodborne Pathogens.2 Biosafety Level 23 or other
appropriate biosafety practices4,5 should be used for materials that
contain or are suspected of containing infectious agents.
• The following warnings and precautions apply to
:
DANGER. Contains sodium hydroxide.
Hazard
H314
Causes severe skin burns and eye
damage.
H290
May be corrosive to metals.
Prevention
P234
Keep only in original container.
P260
Do not breathe mist/vapors/spray.
P264
Wash hands thoroughly after handling.
P280
Wear protective gloves/protective
clothing/eye protection.
Response
P301+P330+P331 IF SWALLOWED: Rinse mouth. Do NOT
induce vomiting.
P303+P361+P353 IF ON SKIN (or hair): Remove/take off
immediately all contaminated clothing.
Rinse skin with water/shower.
P304+P340
IF INHALED: Remove victim to fresh
air and keep at rest in a position
comfortable for breathing.
P305+P351+P338 IF IN EYES: Rinse cautiously with water
for several minutes. Remove contact
lenses, if present and easy to do.
Continue rinsing.
P310
Immediately call a POISON CENTER or
doctor/physician.
P363
Wash contaminated clothing before
reuse.
P390
Absorb spillage to prevent material
damage.
Storage
P405
Store locked up.
P406
Store in corrosive resistant container with
a resistant inner liner.
This material and its container must be disposed of in a safe way.
SUMMARY AND EXPLANATION OF TEST
Lithium is used in the treatment of manic depressive psychosis. Lithium
acts on the neurotransmitters and produces a sedative effect on the
central nervous system. Elevated lithium levels can cause toxicity. Early
symptoms of toxicity include apathy, sluggishness, drowsiness, lethargy,
speech difficulties, tremor, muscle weakness, and ataxia.
Long-term lithium therapy has been reported to cause
hyperparathyroidism in some individuals, with resulting hypercalcemia.1
PRINCIPLES OF PROCEDURE
The MULTIGENT Lithium assay (Lith) uses a spectrophotometric
method. Lithium present in the sample reacts with a substituted
porphyrin compound at an alkaline pH, resulting in a change of
absorbance which is directly proportional to the concentration of
lithium in the sample.
Methodology: Colorimetric
REAGENTS
Reagent Kit
8L25-30, MULTIGENT Lithium is supplied as a liquid, ready-to-use,
single reagent kit which contains:
2 x 20 mL
Estimated tests per kit: 194
Calculation is based on the minimum reagent fill volume per kit.
Reactive Ingredients
Concentration
EDTA
0.05 mmol/L
0.02 mmol/L
Substituted Porphyrin
Nonreactive Ingredients:
contains stabilizer and sodium azide
(< 0.1%) as a preservative.
REAGENT HANDLING AND STORAGE
Reagent Handling
LITHIUM
8L25-30
Symbols in Product Labeling
Calibrator
Concentration
Contents of kit
Contains sodium azide. Contact with acids
liberates very toxic gas.
For product questions contact Abbott Laboratories Customer Support
United States:
1-877-4ABBOTT
Canada:
1-800-387-8378 (English speaking customers)
1-800-465-2675 (French speaking customers)
International:
Call your local Abbott representative
Identifies products to be used together
Ingredients
In vitro diagnostic medical device
•
Ready for use.
• Remove air bubbles, if present in the reagent cartridge, with a
new applicator stick. Alternatively, allow the reagent to sit at the
appropriate storage temperature to allow the bubbles to dissipate.
To minimize volume depletion, do not use a transfer pipette to remove
the bubbles.
CAUTION: Reagent bubbles may interfere with proper detection of
reagent level in the cartridge, causing insufficient reagent aspiration
that could impact results.
Reagent Storage
• Unopened reagents are stable until the expiration date when stored at
2 to 8°C and protected from light. Store MULTIGENT Lithium reagent
in the box.
• Reagent stability is 18 days if the reagent is uncapped and onboard.
Indications of Deterioration
Batch code/Lot number
Instability or deterioration should be suspected if there are visible signs
of leakage, turbidity, microbial growth, or if calibration does not meet
the appropriate package insert and/or ARCHITECT System Operations
Manual criteria.
• The reagent should be clear and dark orange to red.
• Discard reagent if it is turbid or light purple.
Reagent 1
SENTINEL CH. SpA
Via Robert Koch, 2
Milan 20152 Italy
Catalog number/List number
Serial number
Consult instructions for use
Use by/Expiration date
Distributed by
Abbott Laboratories Inc.
Abbott Park, IL 60064 USA
and
ABBOTT
65205 Wiesbaden, Germany
Manufacturer
Temperature limitation
January 2011
8L2530_IFU_01
Protect from light
8/8
1/8
SPECIMEN COLLECTION AND HANDLING
PROCEDURE (Continued)
Suitable Specimens
Manual Dilution Procedure
• Use saline (0.85% to 0.90% NaCl) to dilute the sample.
Example: A manual 1:4 dilution that is run using the Standard dilution
will result in an approximate 1:80 dilution of the sample.
• The operator must enter the manual dilution factor in the patient
or control order screen. The system uses this dilution factor to
automatically correct the concentration by multiplying the result by
the entered factor.
• If the operator does not enter the dilution factor, the result must be
multiplied by the appropriate manual dilution factor before reporting
the result.
NOTE: If the diluted sample result is flagged indicating it is less than
the linear low limit, do not report the result. Rerun using an appropriate
dilution.
For detailed information on ordering dilutions, refer to Section 5 of the
ARCHITECT System Operations Manual.
It is recommended that a standardized 12 hour post dose lithium
concentration be used to assess adequate therapy. Peak concentration
is reached 2 to 4 hours after oral dose.6
• Serum: Use serum collected by standard venipuncture techniques
into plastic tubes with or without gel barriers. Ensure complete clot
formation has taken place prior to centrifugation. When processing
samples, separate serum from blood cells or gel according to the
specimen collection tube manufacturer’s instructions. Glass tubes
were not tested.
Some specimens, especially those from patients receiving
anticoagulant or thrombolytic therapy, may take longer to complete
their clotting processes. Fibrin clots may subsequently form in these
sera and the clots could cause erroneous test results.
• Plasma: Use plasma collected by standard venipuncture techniques
into plastic tubes. Acceptable anticoagulants are sodium heparin
and K2-EDTA. Do not use lithium heparin. Ensure centrifugation is
adequate to remove platelets. When processing samples, separate
plasma from blood cells or gel according to the specimen collection
tube manufacturer’s instructions. Glass tubes were not tested.
For total sample volume requirements, refer to the ASSAY PARAMETERS
section of this package insert and Section 5 of the ARCHITECT System
Operations Manual.
CALIBRATION
Calibration is stable for approximately 5 days (120 hours) and is
required with each reagent cartridge change. Verify calibration with at
least two levels of controls according to the established quality control
requirements for your laboratory. If control results fall outside acceptable
ranges, recalibration may be necessary.
For information on calibrator standardization, refer to
6K30-10
MULTIGENT Clin Chem Cal package insert.
For a detailed description of how to calibrate an assay, refer to Section 6
of the ARCHITECT System Operations Manual.
Specimen Storage
Serum and Plasma
Temperature
Maximum Storage
20 to 25°C
2 to 8°C
-20°C
1 day
7 days
6 months
Bibliographic
Reference
7
7, 8
7
QUALITY CONTROL
As appropriate, refer to your laboratory standard operating procedure(s)
and/or quality assurance plan for additional quality control requirements
and potential corrective actions:
• Two levels of controls (normal and abnormal) are to be run every
24 hours.
• If more frequent control monitoring is required, follow the established
quality control procedures for your laboratory.
• If quality control results do not meet the acceptance criteria defined by
your laboratory, patient values may be suspect. Follow the established
quality control procedures for your laboratory. Recalibration may be
necessary.
• Review quality control results and acceptance criteria following a
change of reagent or calibrator lot.
Guder et al.7 suggest storage of frozen specimens at -20°C for no longer
than the time interval cited above. However, limitations of laboratory
equipment make it necessary in practice for clinical laboratories to
establish a range around -20°C for specimen storage. This temperature
range may be established from either the freezer manufacturer’s
specifications or your laboratory standard operating procedure(s) for
specimen storage.
NOTE: Stored specimens must be inspected for particulates. If present,
mix and centrifuge the specimen to remove particulates prior to testing.
PROCEDURE
Materials Provided
8L25-30 MULTIGENT Lithium
THIS PAGE INTENTIONALLY LEFT BLANK
RESULTS
Refer to Appendix C of the ARCHITECT System Operations Manual for
information on results calculations.
Results for the MULTIGENT Lithium assay are reported in mmol/L, which
are numerically equivalent to mEq/L.
Representative performance data are given in the EXPECTED VALUES
and SPECIFIC PERFORMANCE CHARACTERISTICS sections of this
package insert. Results obtained in individual laboratories may vary.
Materials Required but not Provided
•
6K30-10 MULTIGENT Clin Chem Cal
• Control Material
• Saline (0.85% to 0.90% NaCl) for specimens that require dilution
Assay Procedure
The MULTIGENT Lithium assay uses a standard dilution of approximately
1:20 to achieve optimum analyte levels in the reaction mixture and to
minimize potential interference.
For a detailed description of how to run an assay on the ARCHITECT
c Systems, refer to Section 5 of the ARCHITECT System Operations
Manual.
LIMITATIONS OF THE PROCEDURE
Refer to the REAGENT HANDLING AND STORAGE, SPECIMEN
COLLECTION AND HANDLING, and SPECIFIC PERFORMANCE
CHARACTERISTICS sections of this package insert.
Reagent cross-contamination testing for the MULTIGENT Lithium assay
was performed on an ARCHITECT c System. No ARCHITECT c Systems
assays are affected by MULTIGENT Lithium.
Specimen Dilution Procedure
The ARCHITECT c Systems have an automatic dilution feature; refer to
Section 2 of the ARCHITECT System Operations Manual for additional
information.
Serum and Plasma: Specimens with lithium values exceeding
3.51 mmol/L are flagged and may be diluted by following either the
Automated Dilution Protocol or the Manual Dilution Procedure.
Automated Dilution Protocol
If using the Automated Dilution Protocol, the system performs an
approximate 1:40 dilution of the specimen and automatically corrects the
concentration by multiplying the result by the appropriate dilution factor.
EXPECTED VALUES
Reference Range6
Range (mmol/L)
12 hour post dose (trough)
1.0 to 1.2
concentration
Values greater than 1.5 mmol/L 12 hours post dose indicate a
significant risk of toxicity.
2/8
7/8
SPECIFIC PERFORMANCE CHARACTERISTICS
Method Comparison
Linearity
Correlation studies were performed using CLSI protocol NCCLS EP9-A10
protocol.
Results from the MULTIGENT Lithium assay on an ARCHITECT
c System were compared with the results from a commercially available
colorimetric methodology.
Results from the MULTIGENT Lithium assay on an ARCHITECT
c System were compared with the results from atomic absorption
spectrophotometry (AAS).
Representative results using linear regression analysis are summarized
below.
c System vs.
c System vs.
Comparative Method
AAS
N
60
62
Y - Intercept
-0.006
-0.044
Correlation Coefficient
0.999
0.996
Slope
0.993
1.062
Range (mmol/L)
0.29 to 2.61
0.11 to 3.10
MULTIGENT Lithium is linear from 0.10 to 3.51 mmol/L. Eleven levels
of lithium linearity material were run in triplicate using the MULTIGENT
Lithium assay. A mean of the replicates for each sample was
determined and percent bias calculated. Representative results are
shown below.
Acceptance criteria: ± 5% or 0.075 mmol/L, whichever is greater.
(Mean measured concentration – Theoretical concentration)
%Bias =
x 100
Theoretical concentration
Theoretical
Mean Measured
Bias*
%Bias*
Concentration
Concentration
(mmol/L)
(mmol/L)
(mmol/L)
0.052
0.003
-0.049
-93.6
0.267
0.240
-0.027
-10.3
0.483
0.487
0.004
0.8
0.913
0.950
0.037
4.1
1.343
1.380
0.037
2.8
1.773
1.820
0.047
2.6
2.203
2.233
0.030
1.4
2.634
2.593
-0.040
-1.5
3.064
3.030
-0.034
-1.1
3.494
3.490
-0.004
-0.1
3.924
3.767
-0.158
-4.0
* Bias and %Bias were calculated prior to rounding Theoretical
Concentration and Mean Measured Concentration values.
BIBLIOGRAPHY
1.
2.
3.
Limit of Quantitation (LOQ)
4.
The LOQ for MULTIGENT Lithium is 0.10 mmol/L. The LOQ is the
analyte concentration at which the CV ≤ 20% and the bias is within ± 5%
or 0.075 mmol/L, whichever is greater.
5.
Interfering Substances
THIS PAGE INTENTIONALLY LEFT BLANK
6.
The following compounds, when tested with the MULTIGENT Lithium
assay at the concentrations indicated, resulted in less than 5% or
0.075 mmol/L error (whichever is greater) in detecting lithium.
Lithium
Interferent
Bias
Recovery
Interfering
Concentration
Concentration (mmol/L)
(%)
Substance
(mmol/L)
40 mg/dL
Bilirubin
1.290
0.070
105.4
(684 μmol/L)
1,000
mg/dL
Hemoglobin
1.012
0.019
101.9
(10.0 g/L)
1,500 mg/dL
Intralipid
1.150
0.033
102.9
(15 g/L)
24 mg/dL
Calcium
1.139
0.049
104.3
(6 mmol/L)
1,464
μg/dL
Copper
1.139
0.049
104.3
(230 μmol/L)
1,117
μg/dL
Iron
1.139
0.049
104.3
(200 μmol/L)
6.07
mg/dL
Magnesium
1.139
0.049
104.3
(2.5 mmol/L)
13
mEq/L
Potassium
1.139
0.049
104.3
(13 mmol/L)
350
mEq/L
Sodium
1.139
0.049
104.3
(350 mmol/L)
1,503
μg/dL
Zinc
1.139
0.049
104.3
(230 μmol/L)
7.
8.
9.
10.
TRADEMARKS
The ARCHITECT c System family of instruments consists of c 4000,
c 8000, and c 16000 Systems.
ARCHITECT, c 4000, c 8000, c 16000, c System, MULTIGENT, and
SmartWash are trademarks of Abbott Laboratories in various
jurisdictions.
All trademarks are property of their respective owners.
8L2530_IFU_01
Precision
The precision of the MULTIGENT Lithium assay is ≤ 5% Total CV
or ≤ 0.075 SD, whichever is greater.
Studies were performed using Clinical and Laboratory Standards Institute
(CLSI) protocol NCCLS EP5-A.9 Representative results are summarized
below.
Control
N
Mean (mmol/L)
Within Run
Between Run
Between Day
Total
6/8
SD
%CV
SD
%CV
SD
%CV
SD
%CV
Level 1
80
0.621
0.015
2.36
0.009
1.47
0.029
4.59
0.033
5.37
Level 2
80
0.783
0.015
1.97
0.000
0.00
0.026
3.38
0.031
3.91
Bendz H, Sjödin I, Toss G, et al. Hyperparathyroidism and long-term
lithium therapy—a cross-sectional study and the effect of lithium
withdrawal. J Intern Med 1996;240:357–65.
US Department of Labor, Occupational Safety and Health
Administration. 29 CFR Part 1910.1030. Bloodborne Pathogens.
US Department of Health and Human Services. Biosafety in
Microbiological and Biomedical Laboratories, 5th ed. Washington,
DC: US Government Printing Office, January 2007.
World Health Organization. Laboratory Biosafety Manual, 3rd ed.
Geneva: World Health Organization, 2004.
Sewell DL, Bove KE, Callihan DR, et al. Protection of Laboratory
Workers from Occupationally Acquired Infections; Approved
Guideline—Third Edition (M29-A3). Wayne, PA: Clinical and
Laboratory Standards Institute, 2005.
Burtis CA, Ashwood ER, Bruns DE, editors. Tietz Textbook of Clinical
Chemistry and Molecular Diagnostics, 4th ed. St Louis, MO: Elsevier
Saunders; 2006:1271–2.
Guder WG, da Fonseca-Wollheim F, Heil W, et al. The Quality of
Diagnostic Samples. Darmstadt, Germany: GIT Verlag; 2001:36–7.
US Pharmacopeial Convention, Inc. General notices. In: US
Pharmacopeia National Formulary, 1995 ed (USP 23/NF 18).
Rockville, MD: The US Pharmacopeial Convention, Inc; 1994:11.
Kennedy JW, Carey RN, Coolen RB, et al. Evaluation of Precision
Performance of Clinical Chemistry Devices; Approved Guideline
(EP5-A). Wayne, PA: The National Committee for Clinical Laboratory
Standards, 1999.
Kennedy JW, Carey RN, Coolen RB, et al. Method Comparison
and Bias Estimation Using Patient Samples; Approved Guideline
(EP9-A). Wayne, PA: The National Committee for Clinical Laboratory
Standards, 1995.
Level 3
80
2.391
0.020
0.83
0.000
0.00
0.028
1.15
0.034
1.42
3/8
c Systems Assay Parameters
Lithium Serum/Plasma—Conventional and SI Units
Lithium Serum/Plasma—Conventional and SI Units
Configure assay parameters — General
Configure assay parameters — SmartWash
● General о Calibration
о SmartWash
о Results о Interpretation
Assay: Lith
Type: Photometric
Version: †
Number: 2976
††
Run controls for onboard reagents by: Lot
● Reaction definition
о Reagent / Sample
о Validity checks
Reaction mode: End down
Primary Secondary
Read times
Wavelength: 524 / 476
Main: 8 – 8
Last required read: 8
Absorbance range: 0.0000 – 2.5000
Color correction: ___ – ___
Sample blank type: None
о Reaction definition
о General
о Calibration ● SmartWash о Results
Assay: Lith
COMPONENT REAGENT/ASSAY
WASH
Volume
Trig*
10% Detergent B
345
Cuvette
*Not Required for ARCHITECT software version 7.00 and above.
о Reaction definition
о General
о Calibration
Assay: Lith
Dilution default range:
о SmartWash ● Results о Interpretation
Low-Linearity:
High-Linearity:
о Validity checks
R1
Reagent volume: 160
Water volume: ___
Dispense mode: Type 0
Default
Diluent
Water Dilution factor dilution
115
___ = 1:20.17
●
115
___ = 1:39.60
о
___
___ =
___
о
о Reagent / Sample
Replicates
Configure assay parameters — Results
● Reagent / Sample
Reagent: LITHM
Diluent: Saline
Diluent dispense mode: Type 0
Diluted
Dilution name Sample sample
STD(1:20) : 6.0
6.0
1:40
: 6.0
3.0
_________ : ___
___
о Interpretation
Gender and age specific ranges:**
GENDER
AGE (UNITS)
NORMAL
Assay number: 2976
Result units: mmol/L
0.005§
0.174§
EXTREME
Configure result units
Assay:
Version:
Result units:
Decimal places:
Correlation factor:
Intercept:
● Validity checks
Reaction check: None
Lith
†
mmol/L
3§§ [Range 0 – 4]
1.0000
0.0000
Maximum absorbance variation: ___
Configure assay parameters — Calibration
о General
● Calibration
Assay: Lith
● Calibrators
Calibrator set:
CCC-S
о SmartWash
о Volumes
о Results о Interpretation
Calibration method: Linear
о Intervals
о Validity checks
Calibrator level:
Concentration
Blank: Water
0.000‡
Cal 1: CCC-S1
‡‡
THIS PAGE INTENTIONALLY LEFT BLANK
Replicates: 3 [Range 1 – 3]
о Calibrators
● Volumes
Calibrator: CCC-S
Calibrator level
Blank: Water
Cal 1: CCC-S1
о Calibrators
о Intervals
Diluted
Sample sample
6.0
___
6.0
6.0
о Volumes
о Validity checks
Diluent Water
___
___
115
___
● Intervals
о Validity checks
Calibration intervals:
Full interval: 120 (hours)
Calibration type:
Adjust type: None
о Calibrators
о Volumes
Blank absorbance range:
Span:
Span absorbance range:
Expected cal factor:
Expected cal factor tolerance %:
о Intervals
_____
– _____
Blank
– Blank
_____
– _____
0.00
0
● Validity checks
Due to differences in instrument systems and unit configurations, version numbers may vary.
Parameter is available in ARCHITECT software version 7.00 and above.
Displays the number of decimal places defined in the decimal place field.
Refer to the concentration specified on calibrator labeling or value sheet. In ARCHITECT software version 5.00 and above, these values are
defined on the Configure calibrator set screen.
§ The linear low value (Low-Linearity) is LOQ divided by the Standard dilution factor, then rounded up to the number of decimal places defined
in the decimal places parameter field.
The linear high value (High-Linearity) is Linearity divided by the Standard dilution factor, then rounded down to the number of decimal places
defined in the decimal places parameter field.
** User defined.
§§ Three decimal places are required to provide accurate calculation of linear limits due to the decimal places in the dilution factor.
†
††
‡
‡‡
4/8
5/8