RESUMO
This study presents an accurate and precise analytical strategy for the determination of chloroquine phosphate at trace levels in human body fluids (urine, serum, and saliva). Simultaneous derivatization-spraying based fine droplet formation-liquid phase microextraction (SD-SFDF-LPME) method was used to derivatize and preconcentrate the analyte prior to gas chromatography-mass spectrometry (GC-MS) measurements. Acetic anhydride was employed as derivatizing agent in this study. After optimizing the SD-SFDF-LPME method, the limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.16 and 0.53 mg/kg, respectively. Quadruple isotope dilution (ID4) was coupled to the SD-SFDF-LPME method in order to alleviate matrix effects and promote accuracy/precision of the method. Chloroquine acetamide-d3 was firstly synthesized in our research laboratory and used as the isotopic analogue of the analyte in the ID4 experiments. Superior percent recovery results (99.4% - 101.0%) with low standard deviation values were obtained for the spiked samples. This validated the developed SD-SFDF-LPME-ID4-GC-MS method as highly accurate and precise for the determination of chloroquine phosphate at trace levels. In addition, the isotopic analogue of the analyte was obtained via the acetamide derivative of the analyte, which is an alternative to obtain isotopic analogues of organic compounds that are not accessible or commercially available.
Assuntos
Cloroquina/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Líquida/métodos , Líquidos Corporais/química , Cloroquina/análise , Cloroquina/sangue , Cloroquina/isolamento & purificação , Cloroquina/urina , Humanos , Isótopos , Limite de Detecção , Saliva/químicaRESUMO
Chloroquine, a widely used anti-malaria drug, has gained popularity for the treatment of rheumatoid arthritis, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV). Unfortunately, chloroquine may also negatively impact renal function for patients whose fluid and electrolyte homeostasis is already compromised by diseases. Chronic administration of chloroquine also results in polyuria, which may be explained by suppression of the antidiuretic response of vasopressin. Several of the transporters responsible for concentrating urine are vasopressin-sensitive including the urea transporters UT-A1 and UT-A3, the water channel aquaporin-2 (AQP2), and the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). To examine the effect of chloroquine on these transporters, Sprague-Dawley rats received daily subcutaneous injections of 80 mg·kg(-1)·day(-1) of chloroquine for 4 days. Twenty-four hour urine output was twofold higher, and urine osmolality was decreased by twofold in chloroquine-treated rats compared with controls. Urine analysis of treated rats detected the presence chloroquine as well as decreased urine urea and cAMP levels compared with control rats. Western blot analysis showed a downregulation of AQP2 and NKCC2 transporters; however, UT-A1 and UT-A3 abundances were unaffected by chloroquine treatment. Immunohistochemistry showed a marked reduction of UT-A1 and AQP2 in the apical membrane in inner medullary collecting ducts of chloroquine-treated rats. In conclusion, chloroquine-induced polyuria likely occurs as a result of lowered cAMP production. These findings suggest that chronic chloroquine treatment would exacerbate the already compromised fluid homeostasis observed in diseases like chronic kidney disease.
Assuntos
Cloroquina/efeitos adversos , AMP Cíclico/metabolismo , Capacidade de Concentração Renal/efeitos dos fármacos , Poliúria/induzido quimicamente , Animais , Aquaporina 2/metabolismo , Cloroquina/urina , AMP Cíclico/análise , Regulação para Baixo , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Concentração Osmolar , Ratos , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Membro 1 da Família 12 de Carreador de Soluto , Ureia/urina , Transportadores de UreiaRESUMO
OBJECTIVE: To determine the validity of an antimalarial drug history. DESIGN: During a chloroquine sensitivity study carried out from 27 February to 13 April, 1995, an antimalarial drug history was obtained from the patients. A urine test was used as a gold standard to screen for antimalarial drugs in these patients. SETTING: Two Mutare district primary health care centres. SUBJECTS: Fifty clinical malaria cases were screened. MAIN OUTCOME MEASURES: Cases were classified in a two by two contingency table based on the reported antimalarial drug and the results of the urine test. Positive predictive value and negative predictive value were then examined.
Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Anamnese/normas , Antimaláricos/urina , Cloroquina/urina , Resistência a Medicamentos , Humanos , Programas de Rastreamento , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
Field malaria studies require often the on site detection of chloroquine in urine for monitoring chemoprophylaxis and treatment compliance, investigating drug-use patterns and screening prospective subjects for in vitro and in vivo chemosensitivity tests. The field adapted methods are described, analytical characteristics are compared and different approaches to field adapted assay of chloroquine are discussed.
Assuntos
Cloroquina/urina , Monitoramento de Medicamentos/métodos , Malária Falciparum/tratamento farmacológico , Cloroquina/metabolismo , Cloroquina/uso terapêutico , Cromatografia/métodos , Protocolos Clínicos , Colorimetria/métodos , Interações Medicamentosas , Resistência a Medicamentos , Estudos de Avaliação como Assunto , Hematúria/complicações , Humanos , Concentração de Íons de Hidrogênio , Técnicas Imunoenzimáticas , Malária Falciparum/complicações , Malária Falciparum/psicologia , Malária Falciparum/urina , Nefelometria e Turbidimetria/métodos , Cooperação do Paciente , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Cloroquina/urina , Cromatografia Gasosa-Espectrometria de Massas , Malária/tratamento farmacológico , Plasmodium vivax , Anidridos Acéticos , Animais , Cloroquina/química , Cloroquina/uso terapêutico , Fluoracetatos , Humanos , Malária/urina , Espectrometria de Massas , Controle de QualidadeRESUMO
A specific method for the gas chromatographic determination of chloroquine (CQ) after derivatization with chloroformates, using 9-bromophenanthrene as the internal standard and a column filled with 3% OV-17 on 80-100 mesh Supelcoport is described. Derivatization with chloroformates produced a pyrrolidine derivative, 4-(2-methyl-1-pyrrolidyl)-7-chloroquinoline with CQ, and a carbamate with desethylchloroquine. The chloroformate reaction for CQ is thus selective in the presence of CQ metabolites. The method based on flame ionization detection is highly suitable for quantitation of CQ in urine.
Assuntos
Cloroquina/urina , Aminoquinolinas/análise , Fenômenos Químicos , Química , Cromatografia Gasosa/métodos , Humanos , Espectrometria de Massas , Fosgênio/análogos & derivados , Quinacrina/análiseRESUMO
A method is developed for the gas chromatographic determination of chloroquine after extraction from biological material, using medazepam as the internal standard and a column filled with 3% OV-17 on Gas-Chrom Q. The detection limits are: 0.15 mug/ml of urine, 0.25 mug/ml of whole blood, and 1.50 mug/g of tissue. The technique can be applied in toxicological analysis and in monitoring drug levels.