title: Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies.
abstract: Recent advances in genomics, recombinant expression technologies and peptide synthesis have led to an increased development of protein and peptide therapeutics. Unfortunately this goes hand in hand with a growing market of counterfeit and illegal biopharmaceuticals, including substances that are still under pre-clinical and clinical development. These counterfeit and illegal protein and peptide substances could imply severe health threats as has been demonstrated by numerous case reports. The Belgian Federal Agency for Medicines and Health Products (FAMHP) and customs are striving, together with their global counterparts, to curtail the trafficking and distributions of these substances. At their request, suspected protein and peptide preparations are analysed in our Official Medicines Control Laboratory (OMCL). It stands to reason that a general screening method would be beneficiary in the battle against counterfeit and illegal peptide drugs. In this paper we present such general screening method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of counterfeit and illegal injectable peptide preparations, extended with a subsequent quantification method using ultra-high performance liquid chromatography with diode array detection (UHPLC-DAD). The screening method, taking only 30 min, is able to selectively detect 25 different peptides and incorporates the proposed minimum of five identification points (IP) as has been recommended for sports drug testing applications. The group of peptides represent substances which have already been detected in illegal and counterfeit products seized by different European countries as well as some biopharmaceutical peptides which have not been confiscated yet by the controlling agencies, but are already being used according to the many internet users forums. Additionally, we also show that when applying the same LC gradient, it is also possible to quantify these peptides without the need for derivatization or the use of expensive labelled peptides. This quantification method was successfully validated for a representative subset of 10 different peptides by using the "total error" approach in accordance with the validation requirements of ISO-17025.
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium. Electronic address: Celine.Vanhee@wiv-isp.be.
authors.forename: Celine
authors.initials: C
authors.lastname: Vanhee
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Janvier
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Desmedt
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Goedele
authors.initials: G
authors.lastname: Moens
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Jacques O
authors.initials: JO
authors.lastname: De Beer
authors.affiliation: Division of Food, Medicines and Consumer Safety, Section Medicinal Products, Scientific Institute of Public Health (WIV-ISP), J. Wytsmansstraat 14, B-1050 Brussels, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Courselle
mesh_terms: D001530:Belgium; D002853:Chromatography, Liquid; D058110:Counterfeit Drugs / Q000032:analysis*; D006077:Government Agencies; D010455:Peptides / Q000032:analysis*; D053719:Tandem Mass Spectrometry
chemical_list: D058110:Counterfeit Drugs; D010455:Peptides
keywords: Biopharmaceuticals; Counterfeit medicines; LC–MS/MS; Validation of quantification method