RESUMO
A rapid, sensitive and specific method to quantify cyproheptadine in human plasma using amitriptyline as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using a diethyl-ether/dichloromethane (70/30; v/v) solvent. After removing and drying the organic phase, the extracts were reconstituted with a fixed volume of acetonitrile/water (50/50 v/v)+0.1% of acetic acid. The extracts were analyzed by high performance liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). Chromatography was performed isocratically using an Alltech Prevail C18 5 µm analytical column, (150 mm x 4.6 mm I.D.). The method had a chromatographic run time of 4 min and a linear calibration curve ranging from 0.05 to 10 ng/mL (r2 > 0.99). The limit of quantification was 0.05 ng/mL. This HPLC/MS/MS procedure was used to assess the bioequivalence of cyproheptadine in two cyproheptadine + cobamamide (4 mg + 1 mg) tablet formulations (Cobactin® [cyproheptadine + cobamamide] test formulation supplied from Zambon Laboratórios Farmacêuticos Ltda. and Cobavital® from Solvay Farma (standard reference formulation)). A single 4 mg + 1 mg [cyproheptadine + cobamamide] dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Since the 90% CI for Cmax and AUCs ratios were all within the 80-125% bioequivalence limit proposed by the US Food and Drug Administration, it was concluded that the cyproheptadine test formulation (Cobactin®) is bioequivalent to the Cobavital® formulation for both the rate and the extent of absorption of cyproheptadine.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ciproeptadina/sangue , Ciproeptadina/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Estudos Cross-Over , Ciproeptadina/administração & dosagem , Combinação de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Comprimidos , Equivalência TerapêuticaRESUMO
La intoxicación por ciproheptadina, principal componente de los estimulantes del apetito, se ha transformado en un importante motivo de consulta en los servicios de urgencia a lo largo del país. Estos fármacos, utilizados muchas veces sin prescripción médica, dado su agradable sabor resultan atractivos para los preescolares quienes los ingieren en dosis que sobrepasan el nivel terapéutico, desencadenando cuadros muy variados, que van desde excitación psicomotora hasta la muerte