ANÁLISE DO POTENCIAL DE RISCO À SAÚDE PELA INGESTÃO DE LÍTIO PRESENTE NO MEDICAMENTO CARBONATO DE LÍTIO, UTILIZADO NO TRATAMENTO DO TRANSTORNO BIPOLAR

Abstract

Lithium carbonate is among the most prescribed mood stabilizers worldwide, remaining the first-line pharmacological treatment for bipolar disorder (BD). Although its therapeutic efficacy is widely recognized, it has a narrow therapeutic index, and prolonged or excessive intake can result in renal, neurological, endocrine, and other toxicities. Despite its widespread clinical use, studies that monitor the actual concentration of this metal in pharmaceutical products are extremely scarce. The present study quantified the lithium concentrations in different lithium carbonate formulations available in Brazil to assess their chemical uniformity, estimated daily intake, and potential health risks. Commercial samples were acquired from pharmacies located in Campo Grande/MS and subjected to acid digestion, followed by quantification using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Statistical analysis using the Kruskal-Wallis test revealed significant differences among the formulations (p = 0.012), confirming non-uniform lithium content. The values obtained ranged from 245.47 to 315.24 mg/kg, with the generic medications showing the highest concentrations. The estimated daily intake and the chronic daily intake increased with the therapeutic dose (600-1800 mg/day). The higher dose regimens frequently exceeded the daily exposure allowed by ICH Q3D (R2) (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Harmonised Guideline for elemental impurities) (0.55 mg/day). Furthermore, hazard quotient values above 1 in some of the medication use scenarios indicated potential health risks associated with excessive or long-term exposure to lithium carbonate. As one of the first studies to quantify lithium in commercial formulations, this work highlights the need for systematic monitoring and stricter quality control in production to ensure therapeutic safety.