Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs

Abstract

The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed-phase high-performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C(18) (100 mm × 2.1 mm inside diameter, 2.6 μm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries.

Detection of falsified clopidogrel in the presence of excipients using voltammetry

“…The most widely used analytical techniques for determination of substandard and falsified medicines are based on pharmacopoeia assays. Techniques such as high-performance liquid chromatography (HPLC) with ultraviolet spectroscopy (UV) and/or mass spectrometry detection or gas chromatography [15][16][17] is also widely used. These methods can provide high sensitivity and selectivity but require number of highly technical expensive instruments and expertise.…”

Falsified and substandard cardiovascular drugs in Africa: a need for continued monitoring strategies

“…The dosage method, specially developed for the SEVEN study by a certified public laboratory in France [18] is a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the amount of active ingredient. This kind of method was described [3] as a more advanced level, and bestows several advantages compared to colorimetric techniques, visual inspection, dissolution assays, spectroscopy methods and infrared.…”

Clinical Mass Spectrometry in the Bioinformatics Era: A Hitchhiker’s Guide

“…Injection is followed by reverse phase chromatography and ESI-TOF mass spectrometry operating in positive mode. Most currently-deployed TOF mass spectrometers do not allow for quick polarity-switching; as such, as most common drugs and toxins are best detected with positive ESI, many laboratory would opt for one run with positive ionization [ 195 ], reserving further analysis if the specimen requires analysis for analytes such as frusemide and hydrochlorothiazide [ 201 ], as well as valproic acid [ 202 ] which are detected with negative ESI.

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