Determination of the limitation period for taking drug substances by the hair for the diagnosis of intoxication

Introduction. One of the main advantages of studying human hair over biofluids is that hair analysis allows one to determine the time course of changes in the use of psychoactive substances over several weeks, months, and even years. The role of testing the hair as an alternative, complementary human biomatrix has expanded across the spectrum of toxicological studies. Objective: to identify the possibility of determining the limitation period for taking a drug substance on hair samples from laboratory animals after discontinuing the drug. Material and methods. Phenobarbital and diphenhydramine were model drug substances (MDSs). The investigation was conducted using an Agilent 7890 A/5977 MSD GC/MS sampler. The experiments were done on laboratory animals (red and black male guinea pigs). Hair samples were prepared using the enzymes chymopsin, chymotrypsin, trypsin, and papain. Results. MDSs were detected in the urine of laboratory animals within 12 (phenobarbital) and 4 (diphenhydramine) days after their administration. These substances were found in the hair on 42 days of the experiment after the sample being prepared using the authors’ procedure for enzymatic hydrolysis with the above proteases. Phenobarbital was seen in the amounts comparable to those in the chronic use of the substance, whereas the amount of diphenhydramine was 3-4 times lower than that in chronic intoxication. These results were consistent with the pharmacokinetic characteristics of the substances, with their half-lives and the features of their metabolism. It should be noted that or phenobarbital and diphenhydramine, the amount of the substance detected after 42 days to be greater for red hair than for black one. Conclusion. The procedure for hair sample preparation by enzymatic hydrolysis in combination with GC-MS analysis makes it possible to detect substances in the human biological object, even after urine and blood tests yield negative results. However, the high determination error makes it impossible to quantify.