Alumina Depyrogenates F 18 Fludeoxyglucose Injection during Purification Processes.

Endotoxin indicators (EIs) and photometric bacterial endotoxin test (BET) assays were used to determine the capacity of alumina (Al(2)O(3)) for removing endotoxin from a parenteral solution. Fludeoxyglucose F 18 (FDG) Injection, USP, a radioactive imaging agent, is made daily at about 150 American sites for same-day administration. Each FDG synthesis unit contains a cartridge of alumina for removing a radiochemical impurity before delivery to the final product vial. Recognizing that alumina is a cationic adsorption medium, its capacity for removing endotoxin was challenged with purified endotoxin. A 2000 EU vial of an EI was reconstituted with water or FDG, vortex-mixed, and passed through a representative final product assembly consisting of an alumina cartridge with connecting tubing, a sterilizing membrane filter, and aseptic collection vial. In addition to sterilization, the filter removed alumina "fines" that are inhibitory to the BET because of adsorption of the positive control. Confirmation of labeled claim for each EI and measurement of endotoxin challenge eluates from a simulated FDG process were analyzed by valid kinetic chromogenic assays using a microplate reader and a cartridge reader. Overkill depyrogenation conditions were achieved, defined as greater than a 3 log endotoxin reduction. In conclusion, alumina was observed to depyrogenate the eluate of a representative FDG synthesis unit. LAY ABSTRACT: A fever-inducing (pyrogenic) bacterial toxin may arise during the complex synthesis of a radioactive imaging agent known as Fludeoxyglucose F 18 (FDG) Injection. One of the purification steps for FDG, a cartridge of aluminum oxide (alumina), removes negatively charged, radioactive impurities. Representative FDG solutions were inoculated with purified bacterial endotoxin to determine if the toxin's negative charge would result in removal by alumina. Alumina's effectiveness for endotoxin removal, a process known as depyrogenation, was measured by endotoxin detection assays. Alumina reduced endotoxin levels by more than a thousand fold in a simulated FDG process. Therefore, an unrecognized benefit of the alumina cartridge is removal of a potentially harmful toxin while purifying the FDG for patient injection.

Quality-control analytical methods: endotoxins: essential testing for pyrogens in the compounding laboratory, part 3: a simplified endotoxin test method for compounded sterile preparations.

The first two parts of the IJPC series on endotoxin testing explained the nature of pyrogenic contamination and described various Limulus amebocyte lysate methods for detecting and measuring endotoxin levels with the bacterial endotoxin test described in the United States Pharmacopeia. This third article in that series describes the endotoxin test that is simplest to permorm for pharmacists who prefer to conduct an endotoxin assa at the time of compounding in the pharmacy setting.

Automated endotoxin testing program for high-risk-level compounded sterile preparations at an institutional compounding pharmacy.

PURPOSE: An endotoxin testing program for high-risk-level compounded sterile preparations (CSPs) was verified for compliance with finished-preparation release test requirements of United States Pharmacopeia chapter 797 and implemented at an institutional compounding pharmacy. SUMMARY: An efficient bacterial endotoxins test (BET) was sought for finished-preparation testing of high-risk-level CSPs prepared in batches of > or =25 units. An automated photometric BET was selected that utilized dried, pre-calibrated Limulus amebocyte lysate cartridges rather than liquid reagents and standards. Endotoxin testing began after verifying test conditions for each CSP and approving a standard procedure for training BET analysts and maintaining uniform methodology. A pharmacopeial endotoxin limit and limit dilution were determined for each CSP. The majority of CSPs included patient-controlled analgesia solutions, epidural analgesia solutions, and cardioplegia solutions. BET conditions were verified by measuring the recovery of endotoxin positive controls in sterile water dilutions for each CSP. Cardioplegia solutions met an endotoxin limit of 0.5 EU/mL, and epidural bags had an intrathecal endotoxin limit of 0.05 EU/mL. All other CSPs had detection limits well within compendial requirements. All test results collected during the first year of implementation were pyrogen free, which provided compelling evidence of appropriate application of aseptic technique, appropriate selection of equipment and methods, and the nonpyrogenic quality of powders used in compounding at the pharmacy. CONCLUSION: A photometric endotoxins test that met all requirements of the BET was verified and implemented for high-risk-level CSPs prepared in an institutional pharmacy.

Quality-control analytical methods: endotoxins: essential testing for pyrogens in the compounding laboratory, part2.

Ensuring that the endotoxin burden in sterile preparations is within allowable limits is one of the greatest challenges faced by compounding pharmacists. Today, endotoxin analyses can be performed in the pharmacy with a test kit or accomplished by sending samples to a contract testing laboratory. Both types of screening are discussed in this article, and information that enables compounders to determine the preferred method of endotoxin testing is provided. A brief history of endotoxin testing is presented, and the advantages and disadvantages of pyrogen screening with either an in-house test kit or the services of a contract testing laboratory are explored. Accurate screening for pyrogens ensures that only sterile formulations containing a safe level of endotoxins are dispensed. An essential task in sterile compounding, endotoxin testing safeguards patients against the morbidity and mortality that can result from treatment with a contamination preparation.

Bacterial endotoxin testing: a report on the methods, background, data, and regulatory history of extraction recovery efficiency.

Since the mid-1970s the Limulus Amebocyte Lysate (LAL) assay has been used to test medical devices for bacterial endotoxins. The Association for the Advancement of Medical Instrumentation (AAMI) recently published a standard designated ANSI/AAMI ST 72: 2002, Bacterial Endotoxins--Test methodologies, routine monitoring, and alternatives to batch testing, which addresses LAL testing and associated issues. In order to perform the bacterial endotoxins test (BET), the test article must be extracted in an aqueous medium, with the extract being used as the test solution. In the early years of testing, and periodically throughout LAL test history, questions have arisen about validation of the extraction efficiency of endotoxins from medical devices. The AAMI Microbiological Methods Committee appointed a Task Group to thoroughly research the issue of extraction efficiency and to recommend whether validation of extraction efficiency is necessary for LAL testing of medical devices.

Screening extemporaneously compounded intraspinal injections with the bacterial endotoxins test.

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 kinetic-turbidimetric BET methods to determine valid non-interfering 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 < or = 0.5 mg/mL for baclofen, bupivacaine, clonidine, and morphine and < or = 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 < or = 0.25 mg/mL. The substantial dilution required to overcome test inhibition did not compromise the tests 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.