Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques such as infrared spectroscopy and Raman spectroscopy have always been the first methods of choice to detect counterfeits and illegal preparations, but due to the evolution in the seized products and the necessity of risk assessment, chromatographic methods are becoming more important in this domain. This review intends to give a general overview of the techniques described in literature to characterize counterfeit and illegal pharmaceutical preparations, focusing on the role of chromatographic techniques with different detection tools.

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Chromatography in the Detection and Characterization of Illegal Pharmaceutical Preparations

We review the use of static headspace (S-HS) and dynamic headspace (D-HS) techniques for the extraction of volatiles from different matrices. We present fundamentals and the most relevant advances in instrumentation, together with detailed discussion on the most important parameters affecting HS sampling. We also describe some of the most recent and outstanding applications, classified according to the type of matrix – among them, the use of ionic liquids as solvents for S-HS, the coupling of D-HS to comprehensive two-dimensional gas chromatography, the development of novel miniaturized devices for D-HS sampling and increasing interest in approaches based on HS-mass spectrometry (HS-MS) for fast, unbiased sample classification. We also review multi-step strategies for accurate quantitation of volatiles in samples with noticeable matrix effects. To conclude, we show that HS sampling is a versatile, rapid, efficient, green technique for volatile extraction, free of interferences.

Volatile sampling by headspace techniques

Novel Techniques for Enhancing Sensitivity in Static Headspace

A validated GC-MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules.

Residual solvents play an important role in the synthesis of drugs and in product formulations. In addition, they pose a serious problem, that is toxicity, as many of them exhibit toxic or environmentally hazardous properties. Therefore, constant monitoring of quality control is needed. In this study, we present an overview of regulatory and general methods described by various pharmacopoeias. Then, the most commonly used methodologies for the determination of residual solvents in different pharmaceutical samples are reviewed to demonstrate their limitations, which form the basis of discussion about new methods. Several interesting new alternatives for sample preparation and gas chromatography (GC) separation are presented using examples from recent studies. The techniques described are direct injection, headspace analysis with different modifications and variations, liquid extraction, single-drop microextraction, and solid-phase microextraction. Various GC separation techniques are compared and new solutions to improve sensitivity and efficiency are presented.

Analytical procedures for quality control of pharmaceuticals in terms of residual solvents content: Challenges and recent developments

Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography.

Several gentamicin bulk samples from different origins were investigated using an LC/MS method. LC equipped with ion trap MS with positive ionization was performed on a Capcell Pak C18 (AQ) column with the mobile phase containing 50 mM trifluoroacetic (TFA) and methanol. Impurities present in batches of gentamicin bulk samples were elucidated and compared according to their fragmentation behavior. In total seventeen impurities present in samples, five impurities were not elucidated and two compounds were identified preliminarily. It was observed that the impurity profiles were different in samples from different origins which indicate necessity in the quality control of gentamicin.

Bochu Wang

Papers

Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography.

Impurity analysis of gentamicin bulk samples by improved liquid chromatography-ion trap mass spectrometry