Simultaneous quantification of dexamethasone and 6β-hydroxydexamethasone in rabbit plasma, aqueous and vitreous humor, and retina by UHPLC–MS/MS

Bioanalysis ◽  
2021 ◽  
Author(s):  
Jianghong Gu ◽  
Jiang Wang ◽  
Ashok Krishna ◽  
Lin Xu ◽  
Sharron Stewart ◽  
...  
Keyword(s):  
Rabbit Plasma ◽  
Distribution Profile ◽  
Bioanalytical Method Validation ◽  
Simultaneous Quantification ◽  
In Vivo Release ◽  
The Us ◽  
Fit For Purpose ◽  
Us Fda

Aim: To develop and validate a fit for purpose method for the simultaneous determination of dexamethasone and its major metabolite, 6β-hydroxydexamethasone, in rabbit plasma and ocular matrices to measure the in vivo release and distribution profile of dexamethasone from intravitreal implants. Materials & methods: An UHPLC–MS/MS system was employed to perform the bioanalysis. The method was validated according to the US FDA Bioanalytical Method Validation Guidance for Industry. Results & conclusion: The method was found to be fit-for-purpose for the described biological matrices and had a LLOQ of 0.1 ng/ml.

Quantitative bioanalytical LC–MS/MS assay for S130 in rat plasma-application to a pharmacokinetic study

Bioanalysis ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1469-1481 ◽  
Author(s):  
Yanping Guan ◽  
Yuanyuan Fu ◽  
Yao Liu ◽  
Siyi Wang ◽  
Man Zhao ◽  
...  
Keyword(s):  
Rat Plasma ◽  
Negative Influence ◽  
Selected Reaction Monitoring ◽  
Toxicological Evaluation ◽  
Colorectal Cancer Cells ◽  
The Us ◽  
Us Fda

Aim: An innovative Atg4B inhibitor, S130, exhibited a negative influence on colorectal cancer cells in vitro and in vivo. To assist reliable toxicodynamic and pharmacokinetic evaluation, an LC–MS/MS assay of S130 in rat plasma must be necessary. Results: An LC–MS/MS assay for determination of S130 in rat plasma has been first developed and fully verified whose values met the admissible limits as per the US FDA guidelines. Chromatographic separation was achieved by using an isocratic elution after 3 min. MS was conducted under the ESI+ mode fitted with selected reaction monitoring. The calibration curve proved acceptable linearity over 0.50–800 ng/ml. Conclusion: The developed LC–MS/MS assay of S130 in rat plasma is easily applicable in pharmacokinetics study and the further toxicological evaluation.

The first method for determination of lipoyllysine in human urine after oral lipoic acid supplementation

Bioanalysis ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 1359-1373 ◽  
Author(s):  
Adrianna Kamińska ◽  
Iwona E Głowacka ◽  
Beata Pasternak ◽  
Rafał Głowacki ◽  
Grażyna Chwatko
Keyword(s):  
Acetic Acid ◽  
Lipoic Acid ◽  
Human Urine ◽  
Mobile Phase ◽  
Thiol Group ◽  
Bioanalytical Method ◽  
The Us ◽  
Us Fda ◽  
Reduced Forms

Aim: The first method on urinary excreted amounts of lipoyllysine (LLys) after lipoic acid (LA) supplementation was developed and validated. The suggested procedure allowed simultaneous determination of LLys and LA. Methodology & results: After the conversion of analytes into their reduced forms with tris(2-carboxyethyl)phosphine and derivatization via thiol group with 1-benzyl-2-chloropyridinium bromide, separation of analytes derivatives was performed on C18 column using a gradient mobile phase consisting of acetic acid and acetonitrile. The calibration curves for LA and LLys were linear (R2 > 0.999) in the range of 0.4–12 μM concentration and all validation results were acceptable, according to the US FDA bioanalytical method guidelines. Conclusion: This method was effectively applied for LA and LLys quantification in human urine after oral LA supplementation.

Simultaneous determination of novel ketolide antibiotic nafithromycin and its major metabolite in human plasma using liquid chromatography tandem mass spectrometry

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1767-1776
Author(s):  
Kiran R Patil ◽  
Ravindra D Yeole ◽  
Marcel de Zwart ◽  
Peter Pruim
Keyword(s):  
Phase I ◽  
Human Plasma ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
Simultaneous Quantification ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Us Fda ◽  
Standard Protein

Aim: A sensitive method to quantify nafithromycin and its N-desmethyl metabolite in human plasma was necessary for Phase I pharmacokinetic studies. Methodology: A precise and accurate LC–MS/MS bioanalytical method has been developed and validated for the simultaneous quantification of nafithromycin (NFT, WCK 4873) and N-desmethyl metabolite (M1, WCK 4978) in human plasma. Clarithromycin was used as an internal standard. Protein precipitation technique was used as sample preparation approach. The calibration curve was linear (r ≥ 0.99) over the concentration range of 10–5000 ng/ml for NFT and M1. Method was validated as per US FDA guideline. Conclusion: The proposed method was successfully applied for determination of plasma levels of the NFT and M1 during Phase I clinical studies.

Development and validation of a UPLC–MS/MS method for simultaneous determination of LBPT and its metabolites in human plasma

Bioanalysis ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 211-220
Author(s):  
Mengyi Wu ◽  
Aijing Liu ◽  
Quankun Zhuang ◽  
Ranran Jia ◽  
Yinping Zhou ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Plasma ◽  
Tandem Mass ◽  
Plasma Samples ◽  
Triple Quadrupole ◽  
Multiple Reactions ◽  
The Us ◽  
Us Fda ◽  
Development And Validation

Aim: A UPLC–MS/MS method was developed to determine LBPT as well as its four metabolites in human plasma to support the clinical study aiming to evaluate the efficacy of LBPT tablet in patients undergoing hip/knee replacement. Methodology: Plasma samples were prepared by protein precipitation and then separated on a C18 analytical column using (A) acetonitrile (B) 0.1% formic acid and 10 mM ammonium formate in water. The detection was performed on a triple quadrupole tandem mass spectrometer in positive electrospray ionization using multiple reactions monitoring mode. Results & conclusion: The method has been validated in accordance with the US FDA guidelines and was applied to the measurement of five analytes in human plasma samples from a Phase II clinical trial.

scholarly journals A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1234
Author(s):  
Seunghyun Ahn ◽  
Jung Yeon Lee ◽  
Sang Mi Choi ◽  
Yujeong Shin ◽  
Seyeon Park
Keyword(s):  
Hair Growth ◽  
Dorsal Side ◽  
In Vivo Experiments ◽  
Forkhead Box ◽  
Tocopherol Acetate ◽  
The Us ◽  
Topical Minoxidil ◽  
Fibroblast Growth Factor 10 ◽  
Us Fda

Oral finasteride and topical minoxidil are single components approved by the US FDA for treating hair loss. Some other compounds originating from natural products are also traditionally used for promoting hair growth. In this study, observations of treated keratinocyte cells were used to demonstrate that tocopherol acetate, L-menthol, and stevioside exert an effect on cell regeneration. Furthermore, these were topically applied to the shaved skin of C57BL/6 mice to observe their effects on hair growth. A mixture of tocopherol acetate, L-menthol, and stevioside showed the highest potential for promoting hair growth in vivo. In in vivo experiments, the mixture of tocopherol acetate, L-menthol, and stevioside was more effective than tocopherol acetate or L-menthol alone in promoting hair growth. The transcriptome analysis of skin from the dorsal side of a mouse treated with tocopherol acetate or L-menthol versus vehicle revealed key changes in keratin, keratin-associated protein, forkhead box, sonic hedgehog, fibroblast growth factor 10, desmoglein 4, deoxyribonuclease 1-like 2, and cadherin 3, known to play roles in promoting hair growth.

Developing an isotope dilution UHPLC–MS/MS method to quantify linezolid in human plasma: application to therapeutic drug monitoring

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 991-1001
Author(s):  
Yanping Guan ◽  
Xiaoxia Yu ◽  
Ying Wang ◽  
Qinhai Li ◽  
Dan Liang ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
The Us ◽  
Dosing Regimens ◽  
Us Fda ◽  
Isocratic Mode

Aim: To optimize clinical efficacy and reduce the drug-exposure-related toxicity of linezolid, whose concentrations show wide inter-variabilities, a simple and reliable quantitative assay for therapeutic drug monitoring is necessary. Results: A UHPLC–MS/MS assay has been established for determination of linezolid in human plasma and fully validated according to the US FDA guidelines. After a simple, isotope-dilluted precipitation with methanol, the analytes were separated by a straightforward isocratic mode and the MS/MS was conducted under the ESI+ mode fitted with SRM. The calibration curves proved acceptable linearity in the range of 0.1–30.0 µg/ml. Conclusion: The present assay is currently used in routine clinical practice, being applied to therapeutic drug monitoring and helps to optimize individual dosing regimens and manage adverse effects in ICU patients.

scholarly journals Simultaneous determination of warfarin and 7-hydroxywarfarin in rat plasma by HPLC-FLD

2020 ◽  
Vol 70 (3) ◽  
pp. 343-357 ◽  
Author(s):  
Aref Zayed ◽  
Wahby M. Babaresh ◽  
Ruba S. Darweesh ◽  
Tamam El-Elimat
Keyword(s):  
High Performance ◽  
Direct Determination ◽  
Warfarin Dose ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Bioanalytical Method Validation ◽  
Fda Guidance ◽  
Us Fda ◽  
First Time

AbstractIn this study, high-performance liquid chromatography with fluorescence detection (HPLC-FLD) has been used for the first time, for direct determination of warfarin and its major metabolite, 7-hydroxywarfarin, in rat plasma. The simple and sensitive method was developed using Fortis® reversed-phase diphenyl column (150 × 4.6 mm, 3 μm) and a mobile phase composed of phosphate buffer (25 mmol L−1)/methanol/acetonitrile (70:20:10, V/V/V), adjusted to pH 7.4, at a flow rate of 0.8 mL min−1. The diphenyl chemistry of the stationary phase provided a unique selectivity for separating the structurally related aromatic analytes, warfarin and 7-hydroxywarfarin, allowing their successful quantification in the complex plasma matrix. The method was linear over the range 0.01–25 μg mL−1, for warfarin and 7-hydroxywarfarin, and was found to be accurate, precise and selective in accordance with US FDA guidance for bioanalytical method validation. The method was sensitive enough to quantify 0.01 μg mL−1 of warfarin and 7-hydroxywarfarin (LLOQ) using only 100 μL of plasma. The applicability of this method was demonstrated by analyzing samples obtained from rats after oral administration of a single warfarin dose, and studying warfarin and 7-hydroxywarfarin pharmacokinetics.

Compatibility of immunogenicity guidance by the EMA and the US FDA

Bioanalysis ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 1619-1629 ◽  
Author(s):  
Pekka Kurki
Keyword(s):  
Multidisciplinary Approach ◽  
Reference Product ◽  
Therapeutic Protein ◽  
European Medicines Agency ◽  
Fda Guidance ◽  
Antidrug Antibody ◽  
The Us ◽  
Antibody Assays ◽  
Us Fda

The guidelines for immunogenicity studies by the European Medicines Agency and the US FDA are based on different legislations and regulatory philosophies. In spite of the different background, the main guidelines are compatible on the scientific level, especially for new innovative therapeutic protein products. The importance of sensitive and drug-tolerant antidrug antibody assays and multidisciplinary approach to development and assessment are highlighted by both agencies. The main differences are in the field of biosimilars. The nonclinical in vivo immunogenicity studies are seen more useful by the FDA than by the European Medicines Agency. The draft FDA guidance on interchangeability will complicate global biosimilar development by requiring clinical switch studies with US sourced reference product.

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