Screening extemporaneously compounded intraspinal injections with the bacterial endotoxins test

Abstract

Development of a validated bacterial endotoxins test (BET) method for screening extemporaneously compounded intraspinal injections was studied. In accordance with compendial requirements, interference studies were conducted in injectable-grade intraspinal medications using reagents licensed by the Food and Drug Administration. Positive controls were inoculated into a series of decreasing concentrations of each drug (range, 0.05-4 mg/mL) and tested by gel-clot and kineticturbidimetric BET methods to determine valid noninterfering concentrations. A simplified BET procedure was used for preparing drug samples, inoculating positive controls, conducting the test, and interpreting the results. The most robust test concentrations were ≤0.5 mg/mL for baclofen, bupivacaine, clonidine, and morphine and ≤0.1 mg/mL for hydromorphone. BET interference studies were also done for mixtures of morphine and baclofen, bupivacaine or clonidine. The mixtures were compatible when morphine was diluted to a concentration of ≤0.25 mg/mL. The substantial dilution required to overcome test inhibition did not compromise the test's sensitivity when compared to the endotoxin limit for intraspinal infusions. Validated BET procedures for intraspinal drugs were sufficiently sensitive to assure the absence of endotoxin contamination.