Validation of dry sample devices (Dried Blood Spot) for the therapeutic monitoring of hydroxychloroquine in rheumatic diseases

• Grant number: 21/06616-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2021
• Effective date (End): May 26, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eloisa Silva Dutra de Oliveira Bonfá
• Grantee: Gioanna Zou
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy, AP.TEM

Abstract

Hidroxychloroquine (HCQ) has an exceptional immunomodulatory role in systemic lupus erythematosus (SLE), and subtherapy or withdrawal is associated with disease activation. In adult SLE, it has been reported that HCQ blood concentrations below 1000ng/ml are associated with disease activity and are a strong predictor of exacerbation in the subsequent six months. Therapeutic drug monitoring is additionally performed in serum, plasma or whole blood samples obtained from a venous puncture. Dry sampling devices have been introduced into clinical practice since 1963 for the screening of metabolic diseases in neonates. Since the 1990s, the use of dry sample devices has increased for therapeutic monitoring due to the evolution of bioanalytical methods by liquid chromotography, especially those that are coupled with mass spectrometry. This is because mass spectrometry grants high analytical sensitivity, enabling the quantification of analyses in concentrations on the nanomolar or even picomolar scale. The sampling following this approach confers as benefits, the reduction of costs, since there is no need for collection by professionals. It reduces risks of infections, including in the context of a pandemic such as covid-19, since it is not necessary to perform collections in hospitals. Flexibility is also gained in the collection times, in addition to the easy transport and conservation of the sample. Although the use of these devices is relatively widespread in many developed countries, the use of DBS is not widespread in clinical and laboratory practice in Brazil, especially regarding therapeutic drug monitoring. Therefore, the aim of this project is to validate an innovative approach to therapeutic monitoring of drugs in patients with rheumatologic diseases, starting with the validation of the quantification of hydroxychloroquine in dry sample devices (DBS), using liquid chromatography coupled to mass spectrometry. (AU)