Rapid determination of alprazolam in gin tonic cocktails based on the coupling of IR spectroscopy and chemometrics: A feasibility study

Abstract

“Drug-facilitated sexual assault" (DFSA) is a sexual assault perpetrated against a person rendered unconscious by a substance that changes her/his physical and/or mental condition, such as ethanol or drugs. Several active pharmaceutical ingredients, whether used alone or with alcoholic beverages, can produce anterograde amnesia and loss of inhibition. The most common pharmaceuticals found in DFSAs are GHB (-hydroxybutyric acid), benzodiazepines (Valium, Xanax, or Roipnol), antidepressants (Venlafaxine), muscle relaxants (cyclobenzaprine), antihistamines, sleeping pills (diphenhydramines), hallucinogens, and opioids. Biological samples are typically examined in cases of suspected DFSA; however, occasionally, samples are sent to labs a long period after being collected, jeopardizing the accuracy of the analysis. As a result, in recent years, the focus has shifted to directly detecting the presence of drugs in alcoholic beverages. In light of this, the purpose of the current study is to build a FT-IR-based approach for the determination of alprazolam in a common long drink (gin and tonic). To achieve this goal, pure (Class Pure) and spiked gin tonics (Class Spiked) were analyzed by Fourier-transform infrared spectroscopy (FT-IR). Afterward, two classifiers were used: Sequential preprocessing through ORThogonalization Linear Discriminant Analysis (SPORT-LDA) and Soft Independent Modeling of Class Analogies (SIMCA). Both approaches provided good results: SPORT-LDA achieved a 95% and a 98% accuracy rate (on the external test set of samples) for spiked and pure cocktails, respectively. This corresponds to the misclassification of 5 spiked and 1 pure drinks. The SIMCA model of class pure achieved 98.2% and 91.7% of specificity and sensitivity, respectively, coinciding with 55 pure samples (over 60) correctly accepted and 2 (over 110) erroneously rejected by the model. In conclusion, the SIMCA model of class pure seems preferable, because it minimizes the type II error. Eventually, the study was circumscribed to the spiked cocktails and a novel SPORT model was used to quantify alprazolam in spiked cocktails. This provided noteworthy results, in fact, it led to a Root Mean Square Error in Prediction (RMSEP) of 0.95, and a R²_pred of 0.98.