title: 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.
authors.affiliation: Laboratories Departement, Agence Générale des Equipements et Produits de Santé, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculty of pharmacy, Paris Sud University, UA 401 Matériaux et Santé, Châtenay-Malabry, France.
authors.forename: Mélisande
authors.initials: M
authors.lastname: Bernard
authors.forename: Wiem
authors.initials: W
authors.lastname: Akrout
authors.forename: Christelle Tran
authors.initials: CT
authors.lastname: Van Buu
authors.forename: Carole
authors.initials: C
authors.lastname: Metz
authors.forename: Marie
authors.initials: M
authors.lastname: Antignac
authors.forename: Najet
authors.initials: N
authors.lastname: Yagoubi
authors.forename: Bernard
authors.initials: B
authors.lastname: Do
mesh_terms: D000349:Africa; D002317:Cardiovascular Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D056148:Chromatography, Reverse-Phase / Q000379:methods / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D002317:Cardiovascular Agents
keywords: Cardiovascular drugs; Counterfeit medicines; Liquid chromatography with mass spectrometry; Quality control; Substandard medicines