In this article we discuss about how to calculate the allowable
endotoxin levels in parenteral preparations.

Pharmacists compounding high-risk sterile preparations from
bulk substances must be proficient in calculating the endotoxin load for the compounded
preparations. The endotoxin load in compounded sterile preparations (CSPs) can
be calculated as follows:

1. Multiply the weight of the patient (in kilograms) times
the allowable endotoxin units (EU) per kilogram (kg) [EU/kg] to obtain the
endotoxin limit per hour for non-intrathecal or for intrathecal medication
delivery.

EU/kg × patient weight (kg) = EL per hour (non-intrathecal)

or

0.2 EU/kg × patient weight (kg) = EL per hour (intrathecal)

2. Obtain the required information for the calculations from
USP–NF or a current EL table. (Threshold pyrogenic dose of 5 EU/kg for most
routes of administration or 0.2 EU/kg for intrathecally administered drugs.)

3. Determine the final volume of the preparation.

4. Input the information on the EL worksheet.

5. Determine the final endotoxin load.

6. Consider the route of administration, and determine if
the calculated value exceeds the value in Step 1.

7. If the calculated value does not exceed the value in Step
1, the compound may be prepared.

8. If the calculated value exceeds the value in Step 1,
check with the prescriber.

The amount of endotoxin present in the sample must be less
than the endotoxin release limit calculated for the given end preparation. If
the endotoxin level is excessive and the parenteral has been dispensed, the
patient’s doctor should be notified, and the patient should be monitored for
characteristic host reactions to pyrogens.

**Example**

1. A 158-lb patient is to receive an intrathecal infusion of
morphine sulfate at a rate of 0.3 mg/h.

The solution will be prepared by diluting Infumorph 200 with
0.9% sodium chloride injection to produce an infusion rate of 2 mL/h.

A. Infumorph 200 is preservative-free morphine sulfate 10
mg/mL in 20-mL ampules. How much Infumorph 200 and 0.9% sodium chloride
injection should be used to prepare a 24-hour infusion?

• 0.3 mg/h × 24 hours = 7.2 mg morphine sulfate

• 7.2 mg × 1 mL/10 mg = 0.72 mL Infumorph 200

• 2 mL/h × 24 h = 48 mL total volume

• 48 mL – 0.72 mL = 47.28 mL 0.9% sodium chloride injection

B. What is the endotoxin load for this preparation?

The USP specifies a limit of 14.29 USP EU/mg of morphine
sulfate in solutions for intrathecal use and a limit of 0.5 EU/mL for solutions
containing 0.5 to 0.9% sodium chloride:

• 7.2 mg × 14.29 EU/mg = 102.89 EU from morphine sulfate

• 47.28 mL × 0.5 EU/mL = 23.64 EU from 0.9% sodium chloride
injection

• Endotoxin load = 102.89 EU + 23.64 EU = 126.53 EU

• 126.53 EU/24 h = 5.27 EU/h

C. Does this limit exceed the allowable EL for an
intrathecal injection for this patient?

The maximum amount of endotoxin in a solution for
intrathecal administration is 0.2 EU/kg/h.

Allowable limit: 0.2 EU/kg/h × 1 kg/2.2 lb × 158 lb = 14.36
EU/h

The endotoxin load in the preparation does not exceed the
allowable limit.

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