ms_07559992190V3.

Elecsys Folate III

MODULAR ANALYTICS E170
cobas e 411
07559992 190 100
cobas e 601
cobas e 602

English ▪ 1st incubation: By incubating 25 µL of sample with the folate

pretreatment reagents 1 and 2, bound folate is released from
System information endogenous folate binding proteins.
For cobas e 411 analyzer: test number 1520
For MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 ▪ 2nd incubation: By incubating the pretreated sample with the ruthenium
analyzers: Application Code Number 721 labeled folate binding protein, a folate complex is formed, the amount of
which is dependent upon the analyte concentration in the sample.
Intended use
▪ 3rd incubation: After addition of streptavidin‑coated microparticles and
Binding assay for the in vitro quantitative determination of folate in human folate labeled with biotin, the unbound sites of the ruthenium labeled
serum and plasma. folate binding protein become occupied, with formation of a ruthenium
The binding assay is intended for use on Elecsys and cobas e labeled folate binding protein‑folate biotin complex. The entire complex
immunoassay analyzers. becomes bound to the solid phase via interaction of biotin and
streptavidin.
Summary
Folate belongs to the family of B‑group vitamins composed of an aromatic ▪ The reaction mixture is aspirated into the measuring cell where the
pteridine ring linked through a methylene group to p‑aminobenzoic acid and microparticles are magnetically captured onto the surface of the
a glutamate residue. Folate (folic acid) is vital for normal cellular functions electrode. Unbound substances are then removed with
and plays an essential role in nucleic acid synthesis, methionine ProCell/ProCell M. Application of a voltage to the electrode then induces
regeneration, shuttling and redox reactions of one‑carbon units required for chemiluminescent emission which is measured by a photomultiplier.
normal metabolism and regulation.1,2 ▪ Results are determined via a calibration curve which is instrument-
The folate metabolism can be exemplified as a cycle, where folate specifically generated by 2‑point calibration and a master curve provided
facilitates the transfer of one‑carbon units from one molecule to another via the reagent barcode or e‑barcode.
required in various biochemical reactions: for example, tetrahydrofolate Reagents - working solutions
(THF) accepts a single carbon unit from serine, which is reduced in a The reagent rackpack (M, R1, R2) and the pretreatment reagents (PT1,
number of steps to 5‑methyltetrahydrofolate (5‑MTHF). 5‑MTHF gives its PT2) are labeled as Fol III.
methyl group to homocysteine, which is - with involvement of methionine
synthase and vitamin B12 - enzymatically converted to methionine. The PT1 Pretreatment reagent 1 (white cap), 1 bottle, 4 mL:
resulting THF starts again the cycle of methyl group synthesis. From
methionine, the methyl groups are transferred to S‑adenosylmethionine Sodium 2-mercaptoethanesulfonate (MESNA) 40 g/L, pH 5.5.
(SAM).3 SAM serves as a methyl group donor in several methylation
reactions, like DNA, RNA and protein methylation.1 PT2 Pretreatment reagent 2 (gray cap), 1 bottle, 5 mL:
The methionine cycle is highly sensitive to folate deficiency: with a low Sodium hydroxide 25 g/L.
folate status, the ability of the cell to re-methylate homocysteine is impaired M Streptavidin-coated microparticles (transparent cap), 1 bottle,
and this results in increased homocysteine concentrations in plasma.2
6.5 mL:
Folate also plays an essential role in the synthesis of purine and pyrimidine
precursors of nucleic acids. Altered distribution of methyl groups and Streptavidin-coated microparticles 0.72 mg/mL; preservative.
impaired DNA synthesis play an essential role in the development of
cancers. Abnormal folate status has also been linked with the development R1 Folate binding protein~Ru(bpy) (gray cap), 1 bottle, 9 mL:
of diseases like cardiovascular diseases, neural tube defects, cleft lip and Ruthenium labeled folate binding protein 75 µg/L; human serum
palate, late pregnancy complications, neurodegenerative and psychiatric albumin (stabilizer); borate/phosphate/citrate buffer 70 mmol/L,
disorders.1,2
pH 5.5; preservative.
Folate belongs to the group of essential vitamins, i.e. it cannot be
synthesized by the human organism and therefore must be absorbed from R2 Folate~biotin (black cap), 1 bottle, 8 mL:
diet. Primary sources of folates are green and leafy vegetables, sprouts, Biotinylated folate 17 µg/L; biotin 120 µg/L; human serum albumin
fruits, brewer’s yeast and liver.1,2
(stabilizer); borate buffer 100 mmol/L, pH 9.0; preservative.
Folate deficiency can be caused by decreased nutritional intake, poor
absorption of ingested folate in the intestine or increased demand of folate, Precautions and warnings
for example during physical activity or pregnancy. Deficiency of folate can For in vitro diagnostic use.
also be a result of liver diseases or impaired folate metabolism due to Exercise the normal precautions required for handling all laboratory
genetic defects or drug interactions.2 reagents.
A clinical manifestation of both folate and vitamin B12 deficiency is the so Disposal of all waste material should be in accordance with local guidelines.
called megaloblastic (macrocytic) anemia: due to the affected DNA Safety data sheet available for professional user on request.
synthesis and cell maturation, especially involving the cells of This kit contains components classified as follows in accordance with the
erythropoiesis, the total count of erythrocytes is significantly reduced. The Regulation (EC) No. 1272/2008:
hemoglobin synthesis capacity however is normal, which leads to
abnormally large erythrocyte precursors (“macrocytes” or “megaloblasts”),
which have an elevated hemoglobin content (“hyperchromic anemia”).3,4
Because vitamin B12 and folate are closely interrelated in the cellular
one‑carbon unit metabolism, and also hematologic and clinical
consequences of the two vitamin deficiency states might be similar, it is
advisable to determine both parameters simultaneously in patients with the Danger
relevant symptoms of vitamin deficiency.3,4
H290 May be corrosive to metals.
Test principle
Competition principle. Total duration of assay: 27 minutes. H314 Causes severe skin burns and eye damage.

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H360FD May damage fertility. May damage the unborn child. Criterion: Method comparison serum versus Li‑heparin plasma, slope
0.9‑1.1 + intercept within < ± 2x Limit of Blank (LoB), coefficient of
Prevention: correlation ≥ 0.95.
P201 Obtain special instructions before use. Serum: Stable for 2 hours at 15‑25 °C, 48 hours at 2‑8 °C, 28 days at
‑20 °C (± 5 °C). Freeze only once. Protect from light. Store the samples at
P280 Wear protective gloves/ protective clothing/ eye protection/ 2‑8 °C if they cannot be measured immediately.
face protection. Li‑heparin plasma: Stable for 2 hours at 15‑25 °C, 48 hours at 2‑8 °C,
28 days at ‑20 °C (± 5 °C). Freeze only once. Protect from light. Store the
Response: samples at 2‑8 °C if they cannot be measured immediately.
P303 + P361 IF ON SKIN (or hair): Take off immediately all contaminated The sample types listed were tested with a selection of sample collection
+ P353 clothing. Rinse skin with water. tubes that were commercially available at the time of testing, i.e. not all
available tubes of all manufacturers were tested. Sample collection systems
P304 + P340 IF INHALED: Remove person to fresh air and keep from various manufacturers may contain differing materials which could
affect the test results in some cases. When processing samples in primary
+ P310 comfortable for breathing. tubes (sample collection systems), follow the instructions of the tube
Immediately call a POISON CENTER/ doctor. manufacturer.
Samples should not subsequently be altered with additives (biocides,
P305 + P351 IF IN EYES: Rinse cautiously with water for several anti‑oxidants or substances possibly changing the pH of the sample) in
+ P338 minutes. Remove contact lenses, if present and easy to do. order to avoid erroneous folate recovery.
+ P310 Continue rinsing. Immediately call a POISON CENTER/ Centrifuge samples containing precipitates before performing the assay.
doctor. Do not use heat‑inactivated samples.
P308 + P313 IF exposed or concerned: Get medical advice/attention. Ensure the samples, calibrators and controls are at 20‑25 °C prior to
measurement.
Product safety labeling follows EU GHS guidance. Due to possible evaporation effects, samples, calibrators and controls on
Contact phone: all countries: +49-621-7590 the analyzers should be analyzed/measured within 2 hours.
All human material should be considered potentially infectious. All products Note: Hemolysis may significantly increase folate values due to high
derived from human blood are prepared exclusively from the blood of concentrations of folate in red blood cells. Therefore, hemolyzed samples
donors tested individually and shown to be free from HBsAg and antibodies are not suitable for use in this assay. Samples for folate determinations
to HCV and HIV. The testing methods used assays approved by the FDA or should be collected from fasting persons.
cleared in compliance with the European Directive 98/79/EC, Annex II,
List A. Materials provided
However, as no testing method can rule out the potential risk of infection See “Reagents – working solutions” section for reagents.
with absolute certainty, the material should be handled with the same level Materials required (but not provided)
of care as a patient specimen. In the event of exposure, the directives of the ▪ 07560001190, Folate III CalSet, for 4 x 1.0 mL
responsible health authorities should be followed.5,6
Avoid foam formation in all reagents and sample types (specimens, ▪ 05618860190, PreciControl Varia, for 4 x 3.0 mL
calibrators and controls). ▪ 11732277122, Diluent Universal, 2 x 16 mL sample diluent or
Reagent handling 03183971122, Diluent Universal, 2 x 36 mL sample diluent
The reagents in the kit have been assembled into a ready‑for‑use unit that ▪ General laboratory equipment
cannot be separated. ▪ MODULAR ANALYTICS E170 or cobas e analyzer
All information required for correct operation is read in from the respective Accessories for cobas e 411 analyzer:
reagent barcodes.
▪ 11662988122, ProCell, 6 x 380 mL system buffer
Storage and stability
▪ 11662970122, CleanCell, 6 x 380 mL measuring cell cleaning
Store at 2‑8 °C. solution
Do not freeze. ▪ 11930346122, Elecsys SysWash, 1 x 500 mL washwater additive
Store the Elecsys reagent kit upright in order to ensure complete
availability of the microparticles during automatic mixing prior to use. ▪ 11933159001, Adapter for SysClean
▪ 11706802001, AssayCup, 60 x 60 reaction cups
Stability:
▪ 11706799001, AssayTip, 30 x 120 pipette tips
unopened at 2‑8 °C up to the stated expiration date ▪ 11800507001, Clean‑Liner
after opening at 2‑8 °C 56 days (8 weeks) Accessories for MODULAR ANALYTICS E170, cobas e 601 and
on the analyzers 14 days (2 weeks) onboard cobas e 602 analyzers:
or ▪ 04880340190, ProCell M, 2 x 2 L system buffer
28 days (4 weeks) when stored ▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
alternatively in the refrigerator and solution
on the analyzer, with the total time ▪ 03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and
onboard on the analyzer not CleanCell M before use
exceeding 10 x 8 hours ▪ 03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run
finalization and rinsing during reagent change
Specimen collection and preparation
Only the specimens listed below were tested and found acceptable. ▪ 03004899190, PreClean M, 5 x 600 mL detection cleaning solution
Serum collected using standard sampling tubes or tubes containing ▪ 12102137001, AssayTip/AssayCup, 48 magazines x 84 reaction
separating gel. cups or pipette tips, waste bags
Li‑heparin plasma. Li‑heparin plasma tubes containing separating gel can ▪ 03023150001, WasteLiner, waste bags
be used. ▪ 03027651001, SysClean Adapter M
Accessories for all analyzers:

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▪ 11298500316, ISE Cleaning Solution/Elecsys SysClean, In vitro tests were performed on 16 commonly used pharmaceuticals and in
5 x 100 mL system cleaning solution addition on human erythropoietin. No interference with the assay was
Assay found.
For optimum performance of the assay follow the directions given in this It is contraindicated to measure samples of patients receiving therapy with
document for the analyzer concerned. Refer to the appropriate operator’s certain pharmaceuticals, e.g. methotrexate or leucovorin, because of the
manual for analyzer‑specific assay instructions. cross-reactivity of folate binding protein with these compounds.
Resuspension of the microparticles takes place automatically prior to use. Samples with extremely high total protein concentrations
Read in the test‑specific parameters via the reagent barcode. If in (hyperproteinemia) are not suitable for use in this assay. Hyperproteinemia
exceptional cases the barcode cannot be read, enter the 15‑digit sequence may be caused by, but not limited to, the following conditions:
of numbers (except for the cobas e 602 analyzer). Lymphoma7,8, bone marrow disorders such as multiple myeloma,
monoclonal gammopathy of undetermined significance (MGUS),
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers: Waldenström macroglobulinemia, plasmocytoma7,8,9,10,11,12,13,
PreClean M solution is necessary. Amyloidosis13,14. Respective samples may lead to the formation of protein
Bring the cooled reagents to approximately 20 °C and place on the reagent gel in the assay cup, which may cause a run abort. The critical total protein
disk (20 °C) of the analyzer. Avoid foam formation. The system concentration is dependent upon the individual sample composition.
automatically regulates the temperature of the reagents and the In rare cases, interference due to extremely high titers of antibodies to
opening/closing of the bottles. streptavidin and ruthenium can occur. These effects are minimized by
Calibration suitable test design.
Traceability: This method has been standardized against the WHO For diagnostic purposes, the results should always be assessed in
International Standard NIBSC code: 03/178. conjunction with RBC folate, the patient's medical history, clinical
Every Elecsys reagent set has a barcoded label containing specific examination, and other findings.
information for calibration of the particular reagent lot. The predefined Limits and ranges
master curve is adapted to the analyzer using the relevant CalSet. Measuring range
Calibration frequency: Calibration must be performed once per reagent lot 0.6‑20.0 ng/mL or 1.36‑45.4 nmol/L (defined by the Limit of Blank and the
using fresh reagent (i.e. not more than 24 hours since the reagent kit was maximum of the master curve). Values below the Limit of Blank are
registered on the analyzer). reported as < 0.6 ng/mL (< 1.36 nmol/L). Values above the measuring
Calibration interval may be extended based on acceptable verification of range are reported as > 20.0 ng/mL (> 45.4 nmol/L).
calibration by the laboratory. Lower limits of measurement
Renewed calibration is recommended as follows: Limit of Blank, Limit of Detection and Limit of Quantitation
▪ after 1 month (28 days) when using the same reagent lot Limit of Blank = 0.6 ng/mL (1.36 nmol/L)
▪ after 7 days (when using the same reagent kit on the analyzer) Limit of Detection = 1.2 ng/mL (2.72 nmol/L)
▪ as required: e.g. quality control findings outside the defined limits Limit of Quantitation = 2.0 ng/mL (4.54 nmol/L)
Quality control The Limit of Blank, Limit of Detection and Limit of Quantitation were
For quality control, use PreciControl Varia. determined in accordance with the CLSI (Clinical and Laboratory Standards
Institute) EP17‑A requirements.
In addition, other suitable control material can be used.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of
Controls for the various concentration ranges should be run individually at analyte‑free samples over several independent series. The Limit of Blank
least once every 24 hours when the test is in use, once per reagent kit, and corresponds to the concentration below which analyte‑free samples are
following each calibration. found with a probability of 95 %.
The control intervals and limits should be adapted to each laboratory’s The Limit of Detection is determined based on the Limit of Blank and the
individual requirements. Values obtained should fall within the defined standard deviation of low concentration samples. The Limit of Detection
limits. Each laboratory should establish corrective measures to be taken if corresponds to the lowest analyte concentration which can be detected
values fall outside the defined limits. (value above the Limit of Blank with a probability of 95 %).
If necessary, repeat the measurement of the samples concerned. The Limit of Quantitation is defined as the lowest amount of analyte in a
Follow the applicable government regulations and local guidelines for sample that can be accurately quantitated with a total allowable relative
quality control. error of ≤ 20 %.
Calculation It has been determined using low concentration folate samples.
The analyzer automatically calculates the analyte concentration of each Dilution
sample (either in nmol/L or ng/mL). Samples with folate concentrations above the measuring range can be
diluted manually with Diluent Universal. The recommended dilution is 1:2.
Conversion factors: nmol/L x 0.44 = ng/mL The concentration of the diluted sample must be > 8.5 ng/mL or
ng/mL x 2.27 = nmol/L > 19.3 nmol/L. After manual dilution, multiply the results by the dilution
factor 2.
Limitations - interference Expected values
The assay is unaffected by icterus (bilirubin ≤ 496 µmol/L or ≤ 29 mg/dL), Referring to “The American Journal of Clinical Nutrition”15 serum folate (folic
lipemia (Intralipid ≤ 1500 mg/dL), biotin (≤ 86.1 nmol/L or ≤ 21 ng/mL), IgG acid) values were found as follows:
≤ 16 g/L, IgA ≤ 4.0 g/L and IgM ≤ 10 g/L.
Criterion: Recovery within ± 10 % of initial value with samples > 4 ng/mL Sex Age N Median 2.5th-97.5th percentile
and ≤ ± 0.4 ng/mL with samples ≤ 4 ng/mL.
years ng/mL nmol/L ng/mL nmol/L
Hemolysis may significantly increase folate values due to high
concentrations of folate in red blood cells. Therefore, hemolyzed samples Both all 23345 13.0 29.5 4.6-34.8 10.4-78.9
are not suitable for use in this assay. Male all 11387 12.3 27.9 4.5-32.2 10.2-73.0
Samples should not be taken from patients receiving therapy with high
biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin Female all 11958 13.3 30.1 4.8-37.3 10.9-84.5
administration. Both 4-11 3595 17.2 39.0 8.6-37.7 19.5-85.4
No interference was observed from rheumatoid factors up to a Both 12-19 6390 12.1 27.4 5.0-27.2 11.3-61.6
concentration of 1000 IU/mL.
Both 20-59 8689 11.6 26.3 4.4-31.0 10.0-70.2

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Sex Age N Median 2.5th-97.5th percentile cobas e 411 analyzer
years ng/mL nmol/L ng/mL nmol/L Repeatability Intermediate
Both ≥ 60 4671 16.6 37.6 5.6-45.8 12.7-103.8 precision

These values were obtained in the USA during the National Health and Sample Mean SD CV SD CV
Nutrition Examination Survey (NHANES), 1999‑2004. nmol/L nmol/L % nmol/L %
The values shown below were performed on samples from an apparently Human serum 5 40.4 0.999 2.5 1.51 3.7
healthy population, using the Elecsys Folate III assay.
The calculation is based on 404 sera (177 men, 227 women). The age PreciControl Varia1 7.35 0.488 6.6 0.701 9.5
range was between 20 and 65 years. Pregnant or lactating women were PreciControl Varia2 26.3 0.713 2.7 1.28 4.9
excluded. The reference population was selected according to normal
homocysteine values. MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers
N Median 2.5th-97.5th percentile Repeatability Intermediate
ng/mL nmol/L ng/mL nmol/L precision
404 8.94 20.3 3.89-26.8 8.83-60.8 Sample Mean SD CV SD CV

Please note: These values should only be used as a guideline. ng/mL ng/mL % ng/mL %
It should be taken into consideration that differences in the expected values Human serum 1 1.66 0.255 15.4 0.268 16.1
may exist with respect to population and dietary status. Human serum 2 4.10 0.219 5.4 0.303 7.4
Each laboratory should investigate the transferability of the expected values Human serum 3 11.1 0.449 4.1 0.503 4.6
to its own patient population and if necessary determine its own reference
ranges. Human serum 4 12.2 0.454 3.7 0.467 3.8
Folate deficient sample values Human serum 5 16.4 0.502 3.1 0.625 3.8
25 samples considered to be deficienta) in serum folate concentration were PreciControl Varia1 2.34 0.189 8.1 0.228 9.8
assessed using the Elecsys Folate III assay. All samples were found to be
below the 2.5th percentile as given in the table above. PreciControl Varia2 10.1 0.443 4.4 0.489 4.9
a) Folate deficiency was assessed by measurement of serum folate by two commercially
available folate assays. MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers
Specific performance data Repeatability Intermediate
Representative performance data on the analyzers are given below. precision
Results obtained in individual laboratories may differ.
Sample Mean SD CV SD CV
Precision
Precision was determined using Elecsys reagents, pooled human sera and nmol/L nmol/L % nmol/L %
controls in a protocol (EP5‑A2) of the CLSI (Clinical and Laboratory Human serum 1 3.77 0.579 15.4 0.608 16.1
Standards Institute): 2 runs per day in duplicate each for 21 days (n = 84).
The following results were obtained: Human serum 2 9.31 0.497 5.4 0.688 7.4
Human serum 3 25.2 1.02 4.1 1.14 4.6
cobas e 411 analyzer
Human serum 4 27.7 1.03 3.7 1.06 3.8
Repeatability Intermediate
precision Human serum 5 37.2 1.14 3.1 1.42 3.8
Sample Mean SD CV SD CV PreciControl Varia1 5.31 0.429 8.1 0.518 9.8
ng/mL ng/mL % ng/mL % PreciControl Varia2 22.9 1.01 4.4 1.11 4.9
Human serum 1 1.88 0.150 8.0 0.205 10.9 Method comparison
Human serum 2 3.92 0.200 5.1 0.318 8.1 a) A comparison of the Elecsys Folate III assay (traceable to WHO IS
03/178; y) and the Elecsys Folate III assay prior to standardization against
Human serum 3 11.9 0.346 2.9 0.571 4.8 WHO IS 03/178 (x) using clinical samples gave the following correlations
Human serum 4 13.4 0.301 2.2 0.574 4.3 (ng/mL):
Number of samples measured: 113
Human serum 5 17.8 0.440 2.5 0.666 3.7
PreciControl Varia1 3.24 0.215 6.6 0.309 9.5 Passing/Bablok16 Linear regression
PreciControl Varia2 11.6 0.314 2.7 0.566 4.9 y = 1.14x - 1.97 y = 1.11x - 1.77
τ = 0.939 r = 0.994
cobas e 411 analyzer
The sample concentrations were between 2.1 and 18 ng/mL (4.8 and
Repeatability Intermediate 41 nmol/L).
precision b) A comparison of the Elecsys Folate III assay (y) with a commercially
Sample Mean SD CV SD CV available method (x) using clinical samples gave the following correlations
(ng/mL):
nmol/L nmol/L % nmol/L % Number of samples measured: 106
Human serum 1 4.27 0.341 8.0 0.465 10.9
Passing/Bablok16 Linear regression
Human serum 2 8.90 0.454 5.1 0.722 8.1
y = 0.980x - 0.095 y = 1.09x - 0.659
Human serum 3 27.0 0.785 2.9 1.30 4.8
τ = 0.924 r = 0.984
Human serum 4 30.4 0.683 2.2 1.30 4.3
The sample concentrations were between 1.9 and 17 ng/mL (4.3 and
39 nmol/L).
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c) A comparison of the Elecsys Folate III assay on the cobas e 601 A point (period/stop) is always used in this Method Sheet as the decimal
analyzer (y) with the Elecsys Folate III assay on the cobas e 411 separator to mark the border between the integral and the fractional parts of
analyzer (x) using clinical samples gave the following correlations (ng/mL): a decimal numeral. Separators for thousands are not used.
Number of samples measured: 105 Symbols
Passing/Bablok16 Linear regression Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard (for USA: see
y = 1.05x - 0.303 y = 0.981x + 0.143 [Link] for definition of symbols used):
τ = 0.868 r = 0.982 Contents of kit
The sample concentrations were between 1.6 and 19 ng/mL (3.6 and Analyzers/Instruments on which reagents can be used
43 nmol/L).
Reagent
Analytical specificity
The following cross-reactivities were found, tested with folate Calibrator
concentrations of approximately 3.5 ng/mL, 10 ng/mL and 19 ng/mL. Volume after reconstitution or mixing
Cross-reactant Concentration tested Cross-reactivity GTIN Global Trade Item Number
ng/mL %
COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
Amethopterin 750 2.5 Fresenius Kabi AB.
Aminopterin 750 4.4 All other product names and trademarks are the property of their respective owners.
Additions, deletions or changes are indicated by a change bar in the margin.
Folinic acid 750 0.7 © 2018, Roche Diagnostics

References
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polymorphisms and the associated diseases. Gene 2014;533(1):11-20.
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2 Scaglione F, Panzavolta G. Folate, folic acid and [Link]
5-methyltetrahydrofolate are not the same thing. Xenobiotica
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3 Reynolds EH. The neurology of folic acid deficiency. Handb Clin Neurol
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4 Wick M, Pinggera W, Lehmann P. Clinical Aspects and Laboratory. Iron
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7 Wu AHB. Tietz clinical guide to laboratory tests, 4th ed. St. Louis,
Saunders/Elsevier 2006:608-609, 916-917.
8 Paricaud K, Moulis G, Combis MS, et al. Causes of protidemia above
100 g/L. Eur J Intern Med 2014;25:e123.
9 Filippatos TD, Liamis G, Christopoulou F, et al. Ten common pitfalls in
the evaluation of patients with hyponatremia. Eur J Intern Med
2016;29:22-25.
10 Mailankody S, Landgren O. Monoclonal gammopathy of undetermined
significance and Waldenström's macroglobulinemia. Best Pract Res
Clin Haematol 2016;29:187-193.
11 Morel P, Duhamel A, Gobbi P, et al. International prognostic scoring
system for Waldenström macroglobulinemia. Blood
2009;113:4163-4170.
12 Rajkumar SV. Multiple Myeloma. Curr Probl Cancer 2009;33:7-64.
13 Gertz MA. Immunoglobulin light chain amyloidosis: 2016 update on
diagnosis, prognosis, and treatment. Am J Hematol 2016;91:947-956.
14 Wu AHB. Tietz clinical guide to laboratory tests, 4th ed. St. Louis,
Saunders/Elsevier 2006: 916-917, 925.
15 Pfeiffer CM, Johnson CL, Jain RB, et al. Trends in blood folate and
vitamin B-12 concentrations in the United States, 1988-2004. Am J Clin
Nutr 2007;86:718-727.
16 Bablok W, Passing H, Bender R, et al. A general regression procedure
for method transformation. Application of linear regression procedures
for method comparison studies in clinical chemistry, Part III.
J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.
For further information, please refer to the appropriate operator’s manual for
the analyzer concerned, the respective application sheets, the product
information and the Method Sheets of all necessary components (if
available in your country).
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