Incorporation Of Microsampling Techniques In Bioanalytical Assays…
Current pharmacokinetic (PK) and toxicological studies pose an increasing demand on the volume of blood available from study animals, especially when the study involves small rodents. As a response, microsampling techniques have been introduced into bioanalytical studies.
Dried blood spots (DBS) and capillaries are the two most commonly used microsampling techniques. In this presentation, we present how microsampling can generate high quality bioanalytical data and accurate PK profiling, we also present a unique sample handling method utilizing pre-scored capillaries developed by Frontage (PA, USA), and how this overcomes some of the limitations with the conventional capillary microsampling approach.
Comparison of the Quantitative Measurement of Albumin in Human…
Human serum albumin (HSA) is the most abundant protein in human blood plasma. It is comprised of 585 residues with 17 disulfide bonds. Cys34 is its single free thiol group which is thought to act as an oxidant scavenger. Previous chromatographic studies have shown that the HSA-SH fraction of HSA decreases with age; 76% vs. 48%, young vs elderly healthy male subjects, respectively.1,2 The lower percent of SH present is a measure of the frailty of the person. Since ELISA can only measure total albumin, it does not provide a complete assessment of the person’s overall health. Although typical serum albumin levels range from 35-50 mg/mL of serum, lower or higher levels of certain serum albumins indicate disease states (e.g., Cirrhosis of the liver, severe dehydration-kidney disease) which requires treatment. Thus test kits that simply measure the total amount of HSA present in blood plasma may not completely describe the patient condition regarding a measure of frailty of the patient. This poster presents the ability of using LC coupled to high resolution mass spectrometry (HRMS) for the analysis of the different intact albumin proteins.
Development and Validation of an Ultra Sensitive LC-MS/MS Method for…
Midazolam is a widely used central nervous system depressant. It is used for the treatment of insomnia, seizure, and induction of sedation or amnesia for operations. Midazolam is metabolized by cytochrome CYP3A. It is a widely used probing drug for evaluation of CYP3A activity in drug-to-drug interaction (DDI) studies.
Frontage Laboratories Overview Deck 08.2019
We are a CRO providing integrated, scientifically-driven research, analytical and development services throughout the drug discovery and development process to enable biopharmaceutical companies to achieve their drug development goals. We have enabled many innovator, generic and consumer health companies of all sizes to file IND, NDA, ANDA, BLA and 505(b)(2) submissions in global markets allowing for successful development of important therapies and products for patients. We are committed to providing rigorous scientific expertise to ensure the highest quality and compliance. We have successfully assisted clients to advance hundreds of molecules through development to commercial launch in global markets.
Development And Validation Of LC-MS/MS Methods For The…
Guadecitabine (SGI-110), a dinucleotide of β‑decitabine and deoxyguanosine, is currently being evaluated in phase II/III clinical trials for the treatment of hematological malignancies and solid tumors. This article describes the development and validation of bioanalytical assays to quantify guadecitabine and its active metabolite β‑decitabine in human plasma, whole blood and urine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Since β‑decitabine is rapidly metabolized further by cytidine deaminase, plasma and whole blood samples were kept on ice-water after collection and stabilized with tetrahydrouridine (THU) directly upon sample collection. Sample preparation consisted of protein precipitation for plasma and whole blood and dilution for urine samples and was further optimized for each matrix and analyte separately. Final extracts were injected onto a C6-phenyl column for guadecitabine analysis, or a Nova-Pak Silica column for β‑decitabine analysis. Gradient elution was applied for both analytes using the same eluents for each assay and detection was performed on triple quadrupole mass spectrometers operating in the positive ion mode (Sciex QTRAP 5500 and QTRAP 6500). The assay for guadecitabine was linear over a range of 1.0–200 ng/mL (plasma, whole blood) and 10–2000 ng/mL (urine). For β‑decitabine the assay was linear over a range of 0.5–100 ng/mL (plasma, whole blood) and 5–1000 ng/mL (urine). The presented methods were successfully validated according to the latest FDA and EMA guidelines for bioanalytical method validation and applied in a guadecitabine clinical mass balance trial in patients with advanced cancer.
Gene Therapy 2019
Oligonucleotide (OGN) therapy is increasingly recognized as an important therapeutic modality on the promise of curing diseases. However, unlike most biotherapeutics, the development of OGN drugs often requires their determination with high sensitivity and specificity in multiple and complex biologic matrices such as blood and tissues in order to measure their exposure and distribution for understating PK, PD and safety.
At Frontage Laboratories, we have developed highly sensitive and specific quantitative methods for determination of OGN in plasma and tissues using hybridization immunoassay and LC-MS techniques. In this webinar, we will present the method development, validation and the comparison of these techniques for the quantification of OGN as well as a case study with antisense oligonucleotides.