Automated LAL Testing of Parenteral Drugs in the Abbott MS-2

Abstract

A variety of large and small volume parenteral drugs were screened for amenability to automated pyrogen testing with Limulus Amebocyte Lysate (LAL). The multiple spectrophotometer simultaneously incubates up to 88 samples per module at 35 °C, and reads and records the optical density of each reaction mixture at 1 -min intervals. The recorded data were used to define standard endotoxin-LAL reaction kinetics. Each parenteral drug was characterized by whether or not it modified these standard kinetics. Those drugs that did not alter the standard kinetics were testable in the instrument without sample modification. Those drugs that did alter the standard kinetics fell into three categories: they either inhibited the LAL reaction, enhanced the reaction, or precipitated in the presence of LAL. Generally, these drugs became testable after minor modifications such as dilution or adjustment of pH. Some drugs were not testable with this system. The initial and complete characterization of each parenteral drug is extremely important to eliminate apparent false positive or false negative results. The system is ideal for rapid characterization of parenteral drugs and for defining those factors that modify the reaction in the presence of the drug. Methods of characterization and interpretation of data will be stressed in this presentation.