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1.
AAPS J ; 22(2): 55, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152888

RESUMO

Microsampling techniques enable the minimization of blood collection volume from animals and subsequent handling of the blood samples or their derived plasma or serum samples. This offers advantages over conventional large-volume sampling, such as eliminating the need for satellite animals and improving animal welfare aspects, and providing the opportunity for additional assessments in small animals where blood volume constraints limit endpoints. This study evaluated the feasibility of implementation of capillary microsampling (CMS) in a single-dose study in mice with the ultimate goal of enabling its use in toxicology studies. The focus was on the impact of microsampling on toxicokinetic assessment and on the subsequent hematology assessment in the same animal. A seventy (70)-µL blood collection via CMS from the tail vein had a minimal effect on the hematology parameters of mice (strain C57BL/6) in samples taken within 24 h of blood collection. TK parameters were similar in plasma samples collected via CMS and cardiac puncture sampling. A bioanalytical assay was developed which enabled the quantification of concentration of both the parent drug and a metabolite using only 5-µL plasma sample per analysis. Incurred sample reanalysis (ISR), unexpected event investigation, and re-assay were successfully performed on the limited samples (≤ 20 µL) collected from CMS. The results of this study confirmed the feasibility of implementing CMS in regulated mouse toxicity studies and demonstrated that it is possible to eliminate or reduce satellite animals.


Assuntos
Coleta de Amostras Sanguíneas , Eritrócitos/efeitos dos fármacos , Testes Hematológicos , Cauda/irrigação sanguínea , Testes de Toxicidade , Ureia/análogos & derivados , Valina/análogos & derivados , Administração Oral , Animais , Contagem de Eritrócitos , Eritrócitos/metabolismo , Estudos de Viabilidade , Hematócrito , Hemoglobinas/metabolismo , Camundongos Endogâmicos C57BL , Toxicocinética , Ureia/administração & dosagem , Ureia/sangue , Ureia/toxicidade , Valina/administração & dosagem , Valina/sangue , Valina/toxicidade , Fluxo de Trabalho
2.
Bioanalysis ; 10(16): 1261-1272, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29923414

RESUMO

AIM: A ligand-binding assay (LBA) was used to measure exposure of PRM-151, the recombinant form of human pentraxin-2 (PTX-2), a complex pentamer with multiple binding partners. However, the assay showed a lack of dose-dependent exposure in select preclinical species and it could not differentiate the infused PRM-151 from the endogenous PTX-2 in nonhuman primates. MATERIALS & METHODS: Instead of assessing interference from its multiple binding partners, which could be time consuming and laborious, a LC-MS assay avoid of these interference was implemented to measure 'total' drug without the use of immunoaffinity capture reagents. RESULTS & CONCLUSION: The resultant LC-MS data confirmed the original data and the lack of dose-dependent exposure is now understood to be due to the multiple and diverse targets and functions and resultant complex biodistribution rather than an assay artifact.


Assuntos
Bioensaio , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Espectrometria de Massas em Tandem , Sequência de Aminoácidos , Animais , Cromatografia Líquida , Humanos , Ligantes , Farmacocinética , Testes de Toxicidade
3.
Bioanalysis ; 2(8): 1405-14, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21083341

RESUMO

BACKGROUND: A defined approach to develop and validate an LC-MS/MS assay using dried blood spot (DBS) samples is of great interest to many scientists who are adopting this technology. We have evaluated three distinct sample preparation procedures of DBS samples for LC-MS/MS assay development. RESULTS: A new term 'elution efficiency' is introduced to evaluate the effectiveness of eluting compounds from the DBS cards into the liquid phase. Three different types of DBS cards were studied as part of the sample preparation procedures. A DBS LC-MS/MS method was developed, qualified and then applied to a toxicokinetics study. CONCLUSION: Organic extraction and protein precipitation resulted in significant ion suppression and/or enhancement for FTA(®) Classic or FTA(®) Elute cards. Liquid-liquid extraction produced the least ion suppression/enhancement. Both protein precipitation and liquid-liquid extraction effectively eluted the probe compound from the DBS cards under the conditions tested. However, organic extraction by pure solvents resulted in low elution efficiency.


Assuntos
Métodos Analíticos de Preparação de Amostras/métodos , Análise Química do Sangue/métodos , Coleta de Amostras Sanguíneas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Proteínas Sanguíneas/química , Precipitação Química , Dessecação , Farmacocinética , Ratos , Terminologia como Assunto
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