03/27/2014
Solubility Study of Zinc and
Phosphates in PN and IV Fluid
What is that Brown
Precipitate?
Rex Speerhas, RPh, BCNSP
Nutrition Support Clinical Specialist
What is that Brown Precipitate?
Background
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What is that Brown Precipitate?
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PN switched to Dextrose 5% + PN
ingredients until blood cultures are
negative
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Insulin removed
Calcium gluconate removed
Infused over 24 hours
Home Parenteral Nutrition (HPN)
consumers admitted for sepsis
Blood cultures and urine cultures
What is that Brown Precipitate?
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Brown precipitate seen on filter in several
IVs
No record of any history of precipitate in
HPN fluids
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03/27/2014
What is that Brown Precipitate?
What is that Brown Precipitate?
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Filter with precipitate sent for analysis via
electron microscope
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What is your guess as to what it was?
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What is that Brown Precipitate?
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ZINC PHOSPHATE
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The conventional synthesis method of zinc
phosphate consists in its preparation from
an aqueous solution using zinc sulfate and
sodium dihydrogen phosphate according
to the following reaction:
3ZnSO4∙7H2O + 2Na2HPO4∙2H2O →
Zn3(PO4)2∙4H2O + H2SO4 + 2Na2SO4 +
21H2O
Solubility Study of Zinc and
Phosphates in PN and IV Fluid
What is that Brown Precipitate?
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1000 mL
36 mEq
24 mmol
40 mEq
55 mEq
10 ml
1 ml
0.8 mg
120 mcg
10 mg
40 mg
600 mcg
What is that Brown Precipitate?
Like calcium, which precipitates more
readily with phosphates in IV fluids, zinc
does as well.
As divalent cations, both have limited
solubility with phosphates
Dextrose 5%
Magnesium sulfate
Sodium phosphates
Potassium chloride
Sodium acetate
MVI Adult
Multitrace-4 Conc.
Copper
Selenium
Zinc
Famotidine
Octreotide
Zinc phosphate has a solubility product
(Ksp) of 9.0 x 10-33
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Hypothesis: By changing the
concentrations of zinc and phosphates, we
can find the maximum amounts that may
be added together to avoid precipitation.
Aim:
This study will help decide the
maximum levels of zinc (as chloride or
sulfate) and phosphates that can be
admixed in both parenteral nutrition (PN)
and IV fluids with electrolytes
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03/27/2014
Solubility Study of Zinc and
Phosphates in PN and IV Fluid
Zinc phosphate solubility
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Zinc (15 mg) and sodium phosphates (24 mmol)
were admixed in a solution of 5% dextrose with
electrolytes and resulted in a precipitation in the
filter. When repeated, the precipitate
reoccurred.
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When the same solution was admixed without zinc,
the precipitate did not occur.
When the same solution was admixed without
phosphates, the precipitate did not occur.
No precipitate appeared in a PN formula with
same ingredients.
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Original IV Formula: 1000 ml
Dextrose 5%
50 g
Magnesium sulfate
36 mEq
Sodium phosphates
24 mmol
Potassium chloride
40 mEq
Sodium acetate
55 mEq
MVI Adult
10 ml (contains riboflavin phosphate)
Multitrace-4 Conc.
1 ml
Copper
0.8 mg
Selenium
120 mcg
Zinc
10 mg
Famotidine
40 mg
Octreotide
600 mcg
Zinc phosphate solubility
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D5lytes with 15 mg zinc and
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Zinc phosphate solubility
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12 mmol phosphorus (as sodium phosphates)
6 mmol phosphorus (as sodium phosphates)
Continue down in 3 mmol increments until
precipitate disappears. Then increase by
1 mmol until precipitate appears.
D5lytes with 24 mmol phosphorus and
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Continue down in 2 mg increments until
precipitate disappears. Then increase by
1 mg until precipitate appears.
Zinc phosphate solubility
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HPN with 15 mg zinc and
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Zinc phosphate solubility
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27 mmol phosphorus (as sodium phosphates)
30 mmol phosphorus (as sodium phosphates)
Continue up in 3 mmol increments until
precipitate disappears. Then decrease by
1 mmol until precipitate appears
10 mg zinc
5 mg zinc
HPN with 24 mmol phosphorus and
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17 mg zinc
19 mg zinc
Continue up in 2 mg increments until
precipitate disappears. Then decrease by
1 mg until precipitate appears.
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03/27/2014
Zinc phosphate solubility in IV
Fluid
Zinc phosphate solubility in PN
PN: Zinc + Phosphates
NO PRECIPITATION
D5lytes: Zinc + Phosphates
precipitation
60
25
50
20
Zinc (mg)
Zinc (mg)
40
15
Series1
Series1
30
10
20
5
10
0
0
0
0
5
10
15
20
25
50
100
150
200
250
30
Sodum phosphate (mmol)
Sodium phosphate (mmol)
Solubility Study of Zinc and
Phosphates in PN and IV Fluid
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Results:
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Conclusion
All mixtures of zinc and phosphates tested in
D5lytes precipitated.
All mixtures of zinc and phosphates tested in
PN did not precipitate.
The tested pH of the IV fluid and the PN
mixtures was similar.
When switching from HPN to D5 + PN
lytes:
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Remove insulin
Remove calcium
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REMOVE ZINC
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References
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Selected Solubility Products and Formation Constants at
25◦C . Retrieved February 21st, 2011, from
http://www.csudh.edu/oliver/chemdata/data-ksp.htm
Solubility Product Constants, Ksp. Retrieved February
23rd, 2011, from
http://www.chem.purdue.edu/gchelp/howtosolveit/equili
brium/solubility_products.htm
Allwood MC, Greenwood M. Assessment of trace element
compatibility in total parenteral nutrition infusions.
Pharm Weekbl [Sci]. 1992;14(5): 321-324.
Quimby OT, McCune HW. Precipitation of zinc
phosphates from solutions of sodium ortho-, pyro-, and
triphosphate. Anal. Chem. 1957;29(2): 248-253.
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