Detection of counterfeit tablets of an antiviral drug using δ34S measurements by MC-ICP-MS and confirmation by LA-MC-ICP-MS and HPLC-MC-ICP-MS

Abstract

A new approach for pharmaceutical counterfeit detection using laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) and high performance liquid chromatography multicollector inductively coupled plasma mass spectrometry (HPLC-MC-ICP-MS) has been developed. Laser ablation and chromatographic separation parameters have been previously optimised and helium has been used as the carrier gas for better sensitivity. A homogeneity study of 288 pharmaceutical tablets from different batches of the genuine drug has been performed by MC-ICP-MS and characteristic sulfur isotopic signature has been obtained for the genuine product. δ³⁴S measurements by MC-ICP-MS using silicon internal standardisation for the correction of instrumental mass bias effects led to a δ³⁴S of 3.6‰ and an associated combined expanded uncertainty of 1‰ (k = 2).

The active pharmaceutical ingredient (API) of the tablets, a S-containing compound, has been separated by HPLC and sulfur isotope amount ratios have been measured by MC-ICP-MS. δ³⁴S values obtained by HPLC-MC-ICP-MS for the genuine tablets agreed with those obtained by laser ablation MC-ICP-MS, thus confirming that the sulfur isotopic signature is inherent to the S-containing API.

Following the initial development work, a blind exercise was performed for four hundred tablets. The discriminating power of the technique was assessed and uncertainties associated to δ³⁴S values for counterfeit and genuine tablets varied depending on the sample introduction technique utilised. The three approaches were able to differentiate genuine from counterfeit tablets. During the exercise, four distinct groups of counterfeit tablets were detected. The MC-ICP-MS method therefore has potential as a rapid screening tool for pharmaceutical counterfeit detection and classification.