Journal: Development And Validation Of LC-MS/MS Methods For The Quantification Of The Novel Anticancer Agent Guadecitabine And Its Active Metabolite Β Decitabine In Human Plasma, Whole Blood And Urine
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.
Poster: Validation of a Low-Volume Plasma LC-MS/MS Method Using a Capillary Microsampling (CMS) Technique
In recent years there has been much discussion related to the use of fewer animals for pre-clinical safety and efficacy testing. In addition, regulatory agencies have requested testing in pediatric patient populations for all new drug compounds. With the development of more sensitive instrumentation, the need for smaller blood sample size analysis, has been realized. Over the years, techniques such as Dried Blood Spot (DBS) have been utilized to sample less than 50 uL of blood. While DBS seems to work well for many analyses, the historical PK database for most clinical trials has been through the quantitation of drugs from plasma or serum.
Journal: Immunocapture-liquid Chromatography/Mass Spectrometry in Simultaneous Quantification of Total Antibody and ADC for XMT-1522 in Human Plasma
Immunocapture-liquid Chromatography/Mass Spectrometry in Simultaneous Quantification of Total Antibody and ADC for XMT-1522 in Human Plasma.
XMT-1522, an investigational antibody-drug conjugate (ADC) being developed by Mersana Therapeutics and Takeda, represents the first Dolaflexin®-based, cleavable ADC with a high drug-antibody ratio (DAR). Although the drug showed promise in Phase I clinical development, earlier this year Mersana and Takeda agreed to prioritize resources to focus on the advancement of another ADC, XMT-1536, a first-in-class ADC candidate targeting NaPi2b, ending the co-development collaboration for XMT-1522.
Expert Interview: Gene Therapy – Overcoming the Challenges in Bioanalysis of Oligonucleotide-based Therapies and Relevance to the Clinical Development Plan
“Gene therapy provides the hope of actual cures. These therapies still have many challenges to overcome before they will become widely developed therapeutic options.” Featuring Frontage's Chief Business Officer, Hugh Davis, and Vice President of Biologics Services, Weiping Shao
Case Study: A Capillary Microsampling (CMS) Technique for Low Volume Bioanalytical Plasma Analysis in Support of a Regulated Study
Sponsor required development of a Neutralizing Antibody (NAB) method for an antibody drug that interrupts a Ligand: Receptor interaction.Previous attempts to develop a Cell-Based NAB had been unsuccessful and current attempts to develop a Competitive Ligand Binding assay were also having difficulty with method sensitivity, reproducibility and drug tolerance. Pipeline progression for this asset was halted until these issues could be resolved.