Screening Test for Fast Isoniazid Inactivators

A screening test is described for assaying fast inactivators of isoniazid (INH) in serum. Trichioracetic acid filtrates are reacted with a trans-cinnamaldehyde reagent to form a colored hydrazone derivative of INH. The metabolic degradation of the drug is discussed as well as interferences. The color is read at 352-354 mz. I..ECENTLY a coniparison was niade (1-4) of the chemical method of Poole and Meyer (5) and the microbiological test niethods for the determination of isoniazid (1NH) (6-8), demonstrating the sources of errors of tile j)revious procedure. Among chemical methods, the test of Peters (!i) was recommended on account of its high repro-ducibility; however, it requires an expensive instrunient usually not available in clinical laboratories. Excluded from this survey were methods (10-is) miot sensitive enough to measure concentrations lower than 5-10 g./ml., nor was any reference made to the procedure of Malier et a!. (16); however, critical reviews of this method had been published earlier (17-1.9). in our studies, the procedure of Maher (16) and one similar to this, described by us (18), were found useful in the determination of isoniazid (18, 20). These tests are specific for free TNH alid no inter-ference by acetylated 1NH, by hydraziiie hydrate, or p-afllillOsalicylic acid (PAS) was encountered. The disadvantages of these methods are that measurements below the level of 1 are iiot accurate. Fur-thermore, the two-fold shaking, extraction, and separation by ccii-trifugation, while a simple analytical procedure, might prove some-what cumbersome in a routine bacteriological laboratory. A simpler chemical test is described below. This method, althoug