title: A tiered analytical approach for investigating poor quality emergency contraceptives.
abstract: Reproductive health has been deleteriously affected by poor quality medicines. Emergency contraceptive pills (ECPs) are an important birth control method that women can use after unprotected coitus for reducing the risk of pregnancy. In response to the detection of poor quality ECPs commercially available in the Peruvian market we developed a tiered multi-platform analytical strategy. In a survey to assess ECP medicine quality in Peru, 7 out of 25 different batches showed inadequate release of levonorgestrel by dissolution testing or improper amounts of active ingredient. One batch was found to contain a wrong active ingredient, with no detectable levonorgestrel. By combining ultrahigh performance liquid chromatography-ion mobility spectrometry-mass spectrometry (UHPLC-IMS-MS) and direct analysis in real time MS (DART-MS) the unknown compound was identified as the antibiotic sulfamethoxazole. Quantitation by UHPLC-triple quadrupole tandem MS (QqQ-MS/MS) indicated that the wrong ingredient was present in the ECP sample at levels which could have significant physiological effects. Further chemical characterization of the poor quality ECP samples included the identification of the excipients by 2D Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY 1H NMR) indicating the presence of lactose and magnesium stearate.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Monge
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Prabha
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Manshui
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Payne
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Harris
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Blaine
authors.initials: B
authors.lastname: House
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Juggins
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Cizmarik
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, United Kingdom; WorldWide Antimalarial Resistance Network, Churchill Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
authors.affiliation: Product Quality and Compliance, FHI 360, Durham, North Carolina, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D044363:Contraception, Postcoital; D005260:Female; D006801:Humans; D053719:Tandem Mass Spectrometry
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