A Tiered Analytical Approach for Investigating Poor Quality Emergency Contraceptives

Authors
Monge, Maria Eugenia; Dwivedi, Prabha; Zhou, Manshui; Payne, Michael; Harris, Chris; House, Blaine; Juggins, Yvonne; Cizmarik, Peter; Newton, Paul N.; Fernández, Facundo M.; Jenkins, David
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
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 multiplatform 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 (DARTMS) 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.
Fil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. Georgia Institute of Technology. School of Chemistry and Biochemistry; Estados Unidos
Fil: Dwivedi, Prabha. Georgia Institute of Technology. School of Chemistry and Biochemistry; Estados Unidos
Fil: Zhou, Manshui. Georgia Institute of Technology. School of Chemistry and Biochemistry; Estados Unidos
Fil: Payne, Michael. Product Quality and Compliance; Estados Unidos
Fil: Harris, Chris. Product Quality and Compliance; Estados Unidos
Fil: House, Blaine. Product Quality and Compliance; Estados Unidos
Fil: Juggins, Yvonne. Product Quality and Compliance; Estados Unidos
Fil: Cizmarik, Peter. Product Quality and Compliance; Estados Unidos
Fil: Newton, Paul N.. University of Oxford. Churchill Hospital. Centre for Tropical Medicine; Reino Unido. University of Oxford. Churchill Hospital. WorldWide Antimalarial Resistance Network; Reino Unido. Mahosot Hospital. Microbiology Laboratory. Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit; Laos
Fil: Fernández, Facundo M.. Georgia Institute of Technology. School of Chemistry and Biochemistry; Estados Unidos
Fil: Jenkins, David. Product Quality and Compliance; Estados Unidos
Subject
Mass Spectrometry
Liquid Chromatography
Ion Mobility
Nuclear Magnetic Resonance
Contraceptives
Drug quality
Levonorgestrel
Química Analítica
Ciencias Químicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/4103