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1.
Bioanalysis ; 15(16): 955-1016, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37650500

RESUMO

The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on the ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1A) covers the recommendations on Mass Spectrometry and ICH M10. Part 1B covers the Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine. Part 2 (LBA, Biomarkers/CDx and Cytometry) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 15 and 14 (2023), respectively.


Assuntos
Cromatografia , Vacinas , Biomarcadores , Terapia Baseada em Transplante de Células e Tecidos , Espectrometria de Massas , Oligonucleotídeos , Tecnologia
2.
Bioanalysis ; 11(16): 1495-1508, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31502859

RESUMO

Aim: A method to quantitate doravirine (MK-1439) in human plasma has been developed to support human clinical trials designed to evaluate the safety, pharmacokinetics and efficacy of the compound. Methodology & results: The analyte was extracted using liquid-liquid extraction, separated on a reverse phase HPLC column, and detected on an API-4000 mass spectrometer using a Turbo-Ion spray source in positive ionization mode coupled with multiple reaction monitoring mode was used for quantification. The dynamic range for the assay was 0.02-10 ng/ml using 100 µl of human plasma. Conclusion: The assay was found to be sensitive, selective and reproducible and applied to support the doravirine clinical development program.


Assuntos
Análise Química do Sangue/métodos , Cromatografia Líquida de Alta Pressão/métodos , Extração Líquido-Líquido/métodos , Piridonas/sangue , Piridonas/isolamento & purificação , Espectrometria de Massas em Tandem/métodos , Triazóis/sangue , Triazóis/isolamento & purificação , Humanos , Limite de Detecção , Masculino , Piridonas/farmacocinética , Reprodutibilidade dos Testes , Triazóis/farmacocinética
3.
Bioanalysis ; 10(22): 1781-1801, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30488725

RESUMO

The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LC-MS, hybrid ligand binding assay (LBA)/LC-MS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for LC-MS for small molecules, peptides, oligonucleotides and small molecule biomarkers. Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays) are published in volume 10 of Bioanalysis, issues 23 and 24 (2018), respectively.


Assuntos
Biomarcadores/análise , Oligonucleotídeos/análise , Peptídeos/análise , Animais , Cromatografia Líquida , Humanos , Espectrometria de Massas , Philadelphia
4.
Bioanalysis ; 10(15): 1207-1220, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30062907

RESUMO

AIM: Advances in technology have led to a shift for peptide quantification from traditional ligand-binding assays to LC-MS/MS-based analysis, which presents challenges, in other assay sensitivity, specificity and ruggedness, in addition to lacking of regulatory guidance, especially for the hybrid assay format. Methodology & results: This report communicates a strategy that has been employed in our laboratories for method development and assay validation, and exemplified in a case study of MK-2640, a glucose-responsive insulin, in multiple matrices. Intact MK-2640 was monitored, while immunoaffinity purification and SPE were used to support the rat/dog GLP and clinical studies, respectively. The rationale and considerations behind our approach, as well as the acceptance criteria applied to the assay validation are discussed.


Assuntos
Cromatografia Líquida de Alta Pressão , Insulina/análogos & derivados , Peptídeos/sangue , Espectrometria de Massas em Tandem , Animais , Anticorpos Monoclonais/imunologia , Cromatografia de Afinidade , Cães , Meia-Vida , Humanos , Insulina/análise , Insulina/química , Insulina/farmacologia , Insulina de Ação Prolongada/química , Insulina de Ação Curta/química , Insulinas/química , Insulinas/imunologia , Limite de Detecção , Peptídeos/isolamento & purificação , Peptídeos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Extração em Fase Sólida
5.
J Pharm Biomed Anal ; 156: 58-66, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29689469

RESUMO

Volumetric absorptive microsampling (VAMS), a new microsampling technique, was evaluated for its potential in supporting regulated bioanalysis. Our initial assessment with MK-0518 (raltegravir) using a direct extraction method resulted in 45-52% extraction recovery, significant hematocrit (Ht) related bias, and more importantly, unacceptable stability (>15% bias from nominal concentration) after 7-day storage. Our investigation suggested that the observed biases were not due to VAMS absorption, sampling techniques, lot-to-lot variability, matrix effect, and/or chemical stability of the compound, but rather the low extraction recovery. An effort to improve assay recovery led to a modified liquid-liquid extraction (LLE) method that demonstrated more consistent performance, minimal Ht impact (Ht ranged from 20 to 65%), and acceptable sample stability. The same strategy was successfully applied to another more hydrophilic model compound, MK-0431 (sitagliptin). These results suggest that the previously observed Ht effect and "instability" were in fact due to inconsistent extractability, and optimizing the extraction recovery to greater than 80% was critical to ensure VAMS performance. We recommend adding Ht-independent recovery as part of feasibility assessment to de-risk the long-term extractability-mediated stability bias before implementing VAMS in regulated bioanalysis.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Fracionamento Químico/métodos , Teste em Amostras de Sangue Seco/métodos , Raltegravir Potássico/isolamento & purificação , Coleta de Amostras Sanguíneas/instrumentação , Fracionamento Químico/instrumentação , Cromatografia Líquida de Alta Pressão , Teste em Amostras de Sangue Seco/instrumentação , Estabilidade de Medicamentos , Hematócrito , Raltegravir Potássico/sangue , Raltegravir Potássico/química , Padrões de Referência , Fosfato de Sitagliptina/sangue , Fosfato de Sitagliptina/química , Fosfato de Sitagliptina/isolamento & purificação , Espectrometria de Massas em Tandem
6.
J Pharm Sci ; 107(7): 1973-1986, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29548977

RESUMO

Methodology for analysis of a microdosing drug cocktail designed to evaluate the contribution of drug transporters and drug metabolizing enzymes to disposition was developed using liquid chromatography-mass spectrometry-based detection. Fast and sensitive methods were developed and qualified for the quantification of statins (pitavastatin, pitavastain lactone, rosuvastatin, atorvastatin, 2-hydroxy, and 4-hydroxy atorvastatin), midazolam, and dabigatran in human plasma. Chromatographic separation was accomplished using reversed-phase liquid chromatography or hydrophilic interaction liquid chromatography with gradient elution and detection by tandem mass spectrometry in the positive ionization mode using electrospray ionization. The lower limit of quantitation (LLOQ) for the statins assay was 1 pg/mL for the 6 analytes with a linear range from 1 to 1000 pg/mL processing 250 µL plasma sample. The midazolam assay LLOQ was 0.5 pg/mL with a linear range of 0.5 to 1000 pg/mL. For the dabigatran assay, the LLOQ was 10 pg/mL with a linear range of 10 to 5000 pg/mL processing 100 µL plasma sample. The intraday and interday precision and accuracy of the assays were within acceptable ranges, and the assays were successfully applied to support a study where a microdose cocktail was dosed to healthy human subjects for simultaneous assessment of clinical drug-drug interactions mediated by major drug transporters and CYP3A.


Assuntos
Antitrombinas/sangue , Dabigatrana/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Hipnóticos e Sedativos/sangue , Midazolam/sangue , Espectrometria de Massas em Tandem/métodos , Antitrombinas/farmacologia , Cromatografia de Fase Reversa/métodos , Citocromo P-450 CYP3A/metabolismo , Dabigatrana/farmacologia , Interações Medicamentosas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipnóticos e Sedativos/farmacologia , Limite de Detecção , Midazolam/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos
7.
Artigo em Inglês | MEDLINE | ID: mdl-28846865

RESUMO

MK-1293 is a newly approved follow-on/biosimilar insulin glargine for the treatment of Type 1 and Type 2 diabetics. To support pivotal clinical studies during biosimilar evaluation, a sensitive, specific and robust liquid chromatography and tandem mass spectrometry (LC-MS/MS) assay for the simultaneous quantification of glargine and its two active metabolites, M1 and M2 were developed. Strategies to overcome analytical challenges, so as to optimize assay sensitivity and improve ruggedness, were evolved, resulting in a fully validated LC-MS/MS method with a lower limit of quantification (LLOQ) at 0.1ng/mL (∼16pM, equivalent to ∼2.8µU/mL) for glargine, M1 and M2, respectively, using 0.5mL of human plasma. The assay employed hybrid methodology that combined immunoaffinity purification and reversed-phase chromatography followed by electrospray-MS/MS detection operated under positive ionization mode. Stable-isotope labeled 6[D10]Leu-glargine and 4[D10]Leu-M1 were used as internal standards. With a calibration range from 0.1 to 10ng/mL, the intra-run precision (n=5) and accuracy were <6.21%, and 96.9-102.1%, while the inter-run (n=5/run for 7days) precision and accuracy were <9.55% and 96.5-105.1%, respectively, for all 3 analytes. Matrix effect, recovery, analyte stability, and interferences from control matrix, potential concomitant medications and anti-drug antibody were assessed. The assay was fully automated and has been successfully used in support of biosimilar clinical studies. Greater than 94.3% of incurred sample reanalysis (ISR) results met acceptance criteria, demonstrating the robustness of the assay. The strategic considerations during method development and validation are discussed, and can be applied to quantification of other peptides, especially insulin analogs, in the future.


Assuntos
Cromatografia Líquida/métodos , Insulina Glargina/sangue , Insulina Glargina/metabolismo , Espectrometria de Massas em Tandem/métodos , Diabetes Mellitus Tipo 1 , Estabilidade de Medicamentos , Humanos , Insulina Glargina/química , Análise dos Mínimos Quadrados , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Bioanalysis ; 8(22): 2363-2378, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27712081

RESUMO

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This white paper is published in 3 parts due to length. This part (Part 1) discusses the recommendations for small molecules, peptides and small molecule biomarkers by LCMS. Part 2 (Hybrid LBA/LCMS and regulatory inputs from major global health authorities) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in the Bioanalysis journal, issue 23.

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