RESUMO
The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, utilizing thin-layer chromatography (TLC) with a radio-TLC scanner, which also enables the evaluation of product quality. For AQbD, the analytical target profile (ATP), critical quality attributes (CQA), risk management, and the method operable design region (MODR) were defined through response surface methodology to optimize the method using MINITAB® 19 software. This study encompassed the establishment of a control strategy and the validation of the method, including the assessment of selectivity, linearity, precision, robustness, detection limit, quantification limit, range, and the stability of the sample solution. Under the experimental conditions, the method parameters of the TLC scanner were experimentally demonstrated and optimized with an injection volume of 3 µL, a radioactive concentration of 10 mCi/mL, and a carrier volume of 40 µL. Statistical analysis confirmed the method's selectivity for the 131I iodide band Rf of 0.8, a radiochemical impurity IO3- Rf of 0.6, a linearity from 6.0 to 22.0 mCi/mL, and an intermediate precision with a global relative standard deviation (RSD) of 0.624%. The method also exhibited robustness, with a global RSD of 0.101%, a detection limit of 0.09 mCi/mL, and a quantification limit of 0.53 Ci/mL, meeting the prescribed range and displaying stability over time (at 0, 2, and 20 h) with a global RSD of 0.362%, resulting in consistent outcomes. The development of a method based on AQbD facilitated the creation of a design space and an operational space, with comprehensive knowledge of the method's characteristics and limitations. Additionally, throughout all operations, compliance with the acceptance criteria was verified. The method's validity was confirmed under the established conditions, making it suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services.
Assuntos
Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Iodeto de Sódio , Cromatografia em Camada Fina/métodos , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/análise , Radioisótopos do Iodo/análise , Iodeto de Sódio/química , Administração Oral , Reprodutibilidade dos TestesRESUMO
Resumen La diabetes mellitus (DM) es una enfermedad metabólica caracterizada principalmente por signos y síntomas derivados del aumento de glucosa sérica o hiperglucemia. La pandemia por la enfermedad del coronavirus 2019 (COVID- 19) afectó a todo el mundo con informes de pronóstico grave en pacientes diabéticos infectados por el virus del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2) y elevada admisión hospitalaria en la unidad de cuidados intensivos (UCI) en comparación con pacientes no diabéticos. El objetivo del trabajo de revisión bibliográfica fue evaluar y describir algunos de los mecanismos bioquímicos que conducen al pronóstico grave en pacientes con DM infectados por el virus SARS-CoV-2 mediante la búsqueda sistemática de información en diferentes bases de datos. Los resultados mostraron que la elevada admisión a UCI con un pronóstico grave de pacientes diabéticos infectados por el virus fue por presentar inflamación excesiva que ocasiona síndrome de distrés respiratorio agudo, tormenta de citoquinas, neumonía severa, inmunidad deteriorada e hiperglucemia. El virus ingresa a la célula principalmente por la vía endocítica y no endosómica; los receptores celulares centrales implícitos en los mecanismos son receptores de insulina (RI), transportador de glucosa tipo 2 (GLUT-2), dipeptidil-peptidasa-4 (DPP4), transportador de glucosa tipo 4 (GLUT-4), enzima convertidora de angiotensina 2 (ECA2) y el correceptor proteasa transmembrana de serina 2 (TMPRSS2) esencial para la propagación viral. La mayor susceptibilidad a desarrollar COVID- 19 en pacientes diabéticos se debe a la sobreexpresión de ECA2 y las complicaciones graves se incrementan a niveles micro y macrovascular como nefropatías, neuropatías y enfermedades cardiovasculares.
Abstract Diabetes mellitus (DM) is a metabolic disease characterised mainly by signs and symptoms derived from increased serum glucose or hyperglycemia. The coronavirus disease 2019 (COVID-19) pandemic affected the entire world continenwith reports of severe prognosis in diabetic patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and high hospital admissions in the intensive care unit (ICU) compared to non-diabetic patients. The objective of the bibliographic review was to evaluate and describe some of the biochemical mechanisms that lead to severe prognosis in patients with DM infected by the SARSCoV- 2 virus through a systematic search for information in different databases. The results showed that the high ICU admission with a severe prognosis of diabetic patients infected by the virus was due to excessive inflammation that causes acute respiratory distress syndrome, cytokine storm, severe pneumonia, impaired immunity, and hyperglycemia. The virus enters the cell mainly through the endocytic and non-endosomal pathway; the central cellular receptors involved in the mechanisms are insulin receptors (IR), glucose transporter type 2 (GLUT-2), dipeptidyl peptidase-4 (DPP4), glucose transporter type 4 (GLUT-4), glucose converting enzyme angiotensin 2 (ACE2), and the serine transmembrane protease co-receptor 2 (TMPRSS2) essential for viral propagation. The increased susceptibility to developing COVID-19 in diabetic patients is due to the overexpression of ACE2, and serious complications are increased at the microvascular and macrovascular levels, such as nephropathies, neuropathies, and cardiovascular diseases.
Resumo O diabetes mellitus (DM) é uma doença metabólica caracterizada principalmente por sinais e sintomas decorrentes do aumento de glicose sérica ou hiperglicemia. A pandemia pela doença do coronavírus 2019 (COVID-19) afetou o mundo inteiro com relatos de prognóstico grave em pacientes diabéticos infectados pelo vírus da síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2) e altas internações hospitalares na unidade de terapia intensiva (UTI) em comparação com pacientes não diabéticos. O objetivo do trabalho de revisão bibliográfica foi avaliar e descrever alguns dos mecanismos bioquímicos que levam ao prognóstico grave em pacientes com DM infectados pelo vírus SARS-CoV-2 por meio da busca sistemática de informações em diferentes bancos de dados. Os resultados mostraram que a alta admissão na UTI com prognóstico grave de pacientes diabéticos infectados pelo vírus foi devido à inflamação excessiva que apresentavam e que causa síndrome de desconforto respiratório agudo, tempestade de citocinas, pneumonia grave, imunidade prejudicada e hiperglicemia. O vírus entra na célula principalmente pela via endocítica e não endossômica; os receptores celulares centrais envolvidos nos mecanismos são os receptores de insulina (IR), transportador de glicose tipo 2 (GLUT-2), dipeptidil peptidase-4 (DPP4), transportador de glicose tipo 4 (GLUT-4), enzima conversora de angiotensina 2 (ACE2), e o co-receptor protease transmembrana de serina 2 (TMPRSS2) essencial para a propagação viral. A maior suscetibilidade ao desenvolvimento de COVID-19 em pacientes diabéticos deve-se à superexpressão de ECA2, e complicações graves aumentam nos níveis micro e macrovascular, como nefropatias, neuropatias e doenças cardiovasculares.
