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ICP-MS and its use in nutrition

Dr Steph Martin
Consultant Clinical Scientist
Clinical Lead for Specialised Clinical Chemistry
Sheffield
What is ICP-MS
• Inductively
• Coupled
• Plasma
• Mass
• Spectrometer
• Developed in 1980
• First commercially available in 1987
• Becoming increasingly popular in clinical
labs
• Used for elemental and isotope analysis
Why is it so useful?
• Can detect and quantitate most of the elements
in the periodic table
• Can differentiate between different isotopes of
the same element
• Extremely sensitive
• Small sample volumes
• Fast, reasonably automated
• Semi-quantitative mode scans all elements to
identify possible toxicity
General principle
• A plasma is used to
– Obliterate sample into constituent elements
– Ionise the sample into positive ions
• In the MS ions are separated by mass and
detected
A typical ICP-MS
Inside….
The plasma
The plasma
• The plasma is 6000-8000 °C
• Formed by a flow of argon and a strong
electrical current
• Used to instantly breakdown the sample
into constituent elements and form positive
ions
• Made within a quartz tube called the
‘Torch’
Importance of the ionisation potential
The mass spectrometer
• Separates ions by mass: charge ratio
• Contained within a vacuum
• Applies a magnetic field to the ions, only
ions of correct mass will reach the detector
It isn’t perfect
• Polyatomic interferences
• Gadolinium interference on selenium
• Contamination
• Carryover
Polyatomic interferences
• Occurs when 2 ions stick together and have the
same mass as the element we are looking for
• Usually found with argon containing compounds
formed in the plasma
• Examples include:
– 75As (mass 74.92) with 40Ar35Cl (mass 74.93)
– 80Se with 40Ar2
Avoiding interferences
• Using interference equations
– Complex equations using the relative
abundances of the isotope and the ‘doubly
charged’ rate
• Use a different isotope of the same
element (where possible)
• Use a collision gas
Gadolinium
• Used as a radiology contrast media (in CT
and MRI scans)
• Molecular mass 157.25
• Molecular mass of two selenium ions
157.92
• Scan for Gd when assaying selenium
• Allow time for it to be excreted before
collecting sample for selenium assay
Contamination
• Sensitivity of detection means any
contamination can be a problem
• Zinc is very common, found in
– Glass
– Some plastics
– Cosmetics, powdered gloves…..
• Glassware cannot be used!
Contamination
• Chromium is present in stainless steel
– Use of metal needles in venepuncture?
• Some trace elements can be found in
blood tubes
– Managanese particularly affected
– Can be reduced with the use of ‘trace element
free’ blood tubes
Clinical Applications
• Quantitation of specific elements
– e.g. zinc, copper, selenium, cobalt, chromium,
lead, molybdenum, manganese, lithium,
arsenic, aluminium, sodium/chloride (sweat)
• Scanning several elements to identify the
cause of toxicity, if unknown
• Almost any sample type can be used
Monitoring nutrition
• Patients with gastrointestinal disease may
have abnormalities in trace elements
– Increased losses (
– Reduced excretion (
– Reduced absorption
• Patients receiving nutritional support rely
on receiving appropriate supplementation
Manganese
• Manganese is excreted in the bile, in
cholestasis theoretical risk of toxicity
• No case reports of deficiency in PN
patients
• Reduction in recent years of manganese
content of PN additives
Copper
• Copper is excreted in the bile, in
cholestasis theoretical risk of toxicity
• Deficiency is seen in PN patients
• An acute phase reactant
• Symptoms of deficiency include:
– Reduced white cell count, hypochromic
anaemia
Zinc
• Deficiency well documented in PN
patients, if zinc not added to PN
• Deficiency more common in patients with
increased losses via pancreatic or
intestinal fluids
• Symptoms of deficiency include alopecia,
glossitis, skin lesion, poor healing,
confusion
Zinc
• Toxicity has not been documented in PN
patients
• Zinc is a negative acute phase reactant
(sequestered by the liver)
• Bound to albumin in circulation…should
we correct for this?
Selenium
• Deficiency in selenium well documented in
PN patients if selenium not added
• Manifests as cardiomyopathy and skeletal
myopathy
• Toxicity not seen in PN patients (and is
generally very rare)
Chromium
• Deficiency has been seen, but is very rare
– Suitability of assays?
• Excreted in the urine so renal patients
have increased risk of toxicity
• Added to PN solutions but is also a
contaminant
Molybdenum
• No reports of toxicity
• Little in the literature to support monitoring
• Limited case reports of deficiency
Iodine
• No reports of toxicity
• Deficiency possible if not added to PN
solutions
• Lack of definition of requirements
• Deficiency may result in hypothyroidism
Aluminium
• Present as a contaminant in some PN
solutions
• Excreted via kidneys, increased risk in
renal impairment
Monitoring nutrition
• NICE guideline CG32 “Nutrition support for
adults: oral nutrition support, enteral tube
feeding and parenteral nutrition” 2006
(updated 2017)
Additrace
Active ingredients: 1 millilitre of Each ampoule
Additrace contains: contains 10ml of
concentrate.

Ferric chloride 540 µg 20 µmol


Zinc chloride 1.36 mg 100 µmol
Manganese chloride 99.0 µg 5 µmol

Copper chloride 340 µg 20 µmol


Chromic chloride 5.33 µg 0.2 µmol
Sodium selenite 6.9 µg 0.4 µmol
Sodium molybdate 4.85 µg 0.2 µmol

Sodium fluoride 210 µg 50 µmol


Potassium iodide 16.6 µg 1 µmol
NICE recommendations (trace
elements)
Zinc and Baseline. Then every 2–4 weeks, depending on
copper results
Selenium Baseline if risk of depletion. Further testing
dependent on baseline
Manganese Every 3–6 months if on home parenteral nutrition

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