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Calculating
Pharmacy News the Endotoxin Load in Compounded
Compounding Courses,
Symposia, and Event Sterile Preparations
Listings
The purpose
White Papersof this article is to provide a method for calculating the endotoxin load in
compounded sterile preparations. Materials required include the current United States
Pharmacy Products
PharmacopeiaNational
Compounders' Network List Formulary (USPNF) or endotoxin limit table, and a calculator for the
1
equations. The equation to be used is:
Weekly Newsletter
EL = K/M
Book Reviews
where EL
Compounding= Endotoxin
PharmacyLimit
KBook
= theStore
threshold human pyrogenic dose of endotoxin per kilogram (kg) of body weight per
hour, and
M = the maximum recommended human dose/kg of body weight that would be administered in a
SUBSCRIBER
single one-hour period.
RESOURCES
King Guide to Parenteral
The K value is 5.0 EU/kg for parenteral drugs (except those administered intrathecally) and 0.2
Admixtures
EU/kg for Operating
Standard the intrathecal route of administration. The following procedure can be followed prior
toProcedures
the compounding of sterile preparations.
Formulas
The steps in the procedure are as follows:
Physicochemical
Flavorings
1.Discontinued
Multiply the weight of the patient (in kgs) times the allowable endotoxin units (EU) per
Medications
kg Membrane
Filter [EU/kg] to obtain the endotoxin limit per hour for nonintrathecal and intrathecal
medication delivery.1
Compatibility
Oral Vehicles
Examples: Weight
Base-Salt-Ester
Conversion
NaCl Equivalent Values
Veterinary Transdermals
pH Adjustment
Chemotherapy Vial
Reconstitution and Stability
 5.0 EU/kg Patient Weight (kg) = Endotoxin Limit per hour (Nonintrathecal)

or

0.2 EU/kg Patient Weight (kg) = Endotoxin Limit per hour (Intrathecal)

2. Obtain the required information for the calculations from the USPNF or a current
endotoxin limit table.

3. Determine the final volume of the preparation.

4. Input the information on the Endotoxin Limit Worksheet provided herein.

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.

9. If the laboratory-tested result is less than the value in Step 1, the preparation may be
dispensed/administered.

10. If the laboratory-tested result is greater than the value in Step 1, the preparation should be
discarded.

Let's look at an example problem.

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

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

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/hr 24 hrs = 7.2 mg morphine sulfate

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

2 mL/hr 24 hrs = 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 EUs per milligram of morphine sulfate in
solutions for intrathecal use, and a limit of 0.5 endotoxin units per milliliter for solutions
containing 0.5 to 0.9% sodium chloride.1

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 hrs = 5.27 EU/hr

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

The maximum amount of endotoxin in a solution for intrathecal administration is 0.2

EU/kg/hr.2

Allowable limit: 0.2 EU/kg/hr 1 kg/2.2 lbs 158 lbs = 14.36 EU/hr

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

NOTE: Appreciation is extended to Shelly Stockton, PhD, for her calculation example.2

Endotoxin Limit Worksheet

Patient Name: Date:
Patient Weight: Rx No.:
Nonintrathecal Use kg 5 EU/kg = EU Endotoxin Limit/hour
Intrathecal Use kg 0.2 EU/kg = EU Endotoxin Limit/hour

Drug Drug Dose Endotoxin Endotoxin Volume of

Name per 24 Hours x Level = Contribution Drug Used
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________

Vehicle
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________
__________________ ___________ x _________ = __________ ___________

TOTAL

Total Endotoxin Contribution /Total Volume = EU/mL

____________________/_________ = ____________

EU/mL/24 hours = Endotoxin Limit/hour

______ /______ = _____________

References

1. Allen LV Jr. Quality-Control Analytical Methods: Allowable Endotoxin Levels in Sterile

Preparations. IJPC 2004; 8(6): 479-485.

2. Stockton SJ. Calculations. IJPC 2004; 8(6): 468.

Loyd V. Allen, Jr., PhD, RPh

Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy

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EDITORIAL BOARD

Loyd V. Allen, Jr.; International Journal of Pharmaceutical Compounding, Edmond, OK

Lisa D. Ashworth; Children's Medical Center Dallas, Dallas TX

Ron Donnelly; Ottawa Hospital, Ottawa, Canada

Mark Klang; Sloan-Kettering Institute, New York, NY

Ken Latta; Duke University Hospital, Durham, NC

Linda McElhiney; Indiana University Health, Indianapolis, IN

Dave Newton; Bernard J. Dunn School of Pharmacy, Shenandoah University, Winchester, VA

Richard Osteen; Vanderbilt University Medical Center, Nashville, TN

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