Precursor Profiling of Extracted Pseudoephedrine Using Gas Chromatography-Mass Spectrometry (GCMS) in Conjunction with Chemometric Procedure

Abstract

Various methods for the clandestine manufacture of amphetamine-type stimulant (ATS) involve the extraction and subsequent reaction of pseudoephedrine salts with other essential chemicals. The precursor seized in clandestine laboratory operation is supplied from illegal sources or clandestinely extracted from decongestant tablets (despite the presence of excipients that serve to hamper re-extraction). This work reports the organic profiling of pseudoephedrine from a simulated clandestine extract of different decongestant tablets formulations. The study aims to determine the feasibility of the common extraction techniques in removing other excipients to obtain the precursor compound followed by compound identification of the extracted samples by both extraction techniques used namely direct and acid-base extraction. Five different brands of commercially available pseudoephedrine-based decongestant tablets (sample A, B, C, D, and E) at varying strengths were randomly purchased from various commercial pharmacies and reduced to homogenized powder. Samples were then subjected to direct and acid-base extraction procedures. Extracts were subsequently analyzed and profiled using Gas Chromatography-Mass Spectrometer (GCMS) separated using HP-5 MS PDMS column (30m x 250m x 0.25m). Mass spectra were collected with ionization voltage 70 eV, mass range from 40-450 m/z. Data acquisition was obtained with Chemstation software (Agilent, USA) and compounds were identified based on the drug and hydrocarbon library database (NIST 0.6 Version 2.0, USA) and previous literatures. Ethanol solvent recorded the best highest pseudoephedrine yield at 54% for direct simple extraction method from sample B, which was considerably pure as it contains the least excipients compared to the other brands. Meanwhile, acid-base extraction at basic pH in aqueous/diethyl ether (1:2) system at 10 mins agitation recorded higher pseudoephedrine yield (maximum 60.42%) across all the tablets proving that acid-base extraction improved pseudoephedrine purity even for tablets with the complex formulation. Additionally, the GCMS profile reveals the presence of minute excipients within the extracted product. Classification of pseudoephedrine obtained from direct and acid-base methods are shown by principal component analysis (PCA) which account for 77.3% and 78.9% total variation respectively. This information is regarded as chemical profiling useful for forensic intelligence and may assist authorities to combat illegal drug network.