Leading drug developers used Accelerator Mass Spectrometry (AMS) to support almost 20% of the new medicines approved by FDA in 2013 of which Xceleron has been directly involved in supporting 4 of these 5 new drugs. Our clients used 14C tracer / AMS enabled clinical studies that delivered important data whilst saving both time and cost compared to conventional approaches. These studies include the of determination of Absolute Bioavailability and Mass Balance / Metabolism characteristics of the drugs in question. More details on the specific compounds and clinical study designs are expected to become available later this year as the relevant scientific papers are published.
Dr Mike Butler, Xceleron’s CEO said “We are pleased that the many years of effort in supporting our drug developer clients are reflected in the FDA’s approved drug list for 2013. Proper use of the 14C tracer / AMS approach is saving our customers both time and money as it improves the overall efficiency of R&D.”
Ask Xceleron how we can support your drug development efforts using innovative, tried and tested study designs that get results.
In a recent publication in the Journal of Clinical Pharmacology, GSK have published data on the use of [14C] labelled IV microtracer for the determination of absolute bioavailability of dabrafenib in oncology patients. This is the first time that the use of this approach in patients has been published, and it demonstrates the value of the technique for gaining a greater understanding of the fundamental pharmacokinetics. Furthermore, by using this approach GSK were able to shorten the study time frame and it allowed for simultaneous collection of IV and oral pharmacokinetic parameters, thus reducing variability.
Particularly where patients as clinical research participants are concerned, IV microtracer studies offer an innovative and efficient approach for assessing absolute bioavailability and may be applied across a range of therapeutic areas and compound classes.
For further information on this paper and a copy of the abstract, please follow this link
For more information on how this approach can be used in drug development, please do not hesitate to contact Xceleron by email:
Xceleron is pleased to announce that they will be presenting 2 posters in collaboration with Incyte Corp and Neurocrine Biosciences Inc at the forthcoming AAPS Annual Meeting and Exposition to be held in Henry B. Gonzalez Convention Center, San Antonio, from 10th – 14th November 2013.
The Incyte poster (Application of Accelerator Mass Spectrometry in Early Clinical Development; #R6343) describes the use of Accelerator Mass Spectrometry (AMS) for the timely identification of 2 human metabolites that would have been neglected if simple qualitaTIVE LC/MS peak analysis had been used, thus allowing early identification of major metabolites and an early assessment of safety margins in accordance with FDA MIST and ICH M3 regulatory guidance. This poster will be presented between 08:30-11:30 on Thu 14 Nov.
The Neurocrine poster (Confirmation of the Selectivity of an LC+AMS Assay by Cross-Validation with LC MS/MS; Poster #M1360) describes a novel approach to validating the selectivity of LC+AMS by cross validation with a selective LC-MS/MS assay.
Copies of these posters can now be downloaded from our Resources page by clicking on this link.
Published: 14th Annual Land O’Lakes Bioanalytical Conference, 15-18 July 2013
Authors: Connell Cunningham*, Marie Croft*, Anthony R Hall*, David M Higton*, Mark A Seymour*, Rosa Luo†, Evan Smith†, and Ajay Madan†
*: Xceleron Inc, Germantown, MD; †: Neurocrine Biosciences Inc, San Diego, CA
Objectives: Liquid chromatography with Accelerator Mass Spectrometry detection (LC+AMS) is increasingly used as a bioanalytical technique. It is not susceptible to matrix effects and is independent of chemical structure, because the sample graphitization procedure converts all 14C-containing material in samples into a common analyte, solid carbon. It is, therefore, essential that the analyte is chromatographically resolved from any other 14C-containing species. Although the accuracy and precision of a LC+AMS assay is comparable to liquid chromatography with tandem mass spectrometry (LC-MS/MS), the approach to validation of selectivity does differ. This poster describes a novel approach involving cross-validation with a LC MS/MS method.
Methods: Selected plasma samples from a clinical study whereby healthy human subjects received a single oral dose of [14C]-NBI-X were analyzed by LC+AMS. Aliquots of the same samples were independently analysed using a validated LC MS/MS assay, and results obtained from the two orthogonal methods compared.
Results: Selected samples collected from different subjects after dosing were analysed by both methods. The difference between the results was within ± 15% of the mean for all samples, and there was no apparent temporal trend in the data.
Implications: The differences between the concentrations measured by LC+AMS and LC MS/MS in the same sample were well within the known precision of each assay. Thus, it was concluded that the fraction isolated contained no 14C-labelled species other than [14C]-NBI-X and that the LC+AMS assay was highly selective. This methodology is a valuable tool to unambiguously verify the selectivity of LC+AMS assays during method validation.
Published: June, 2013, European Journal of Clinical Pharmacology
Authors: G. Lappin (1), M. J. Boyce (2), T. Matzow (2), S. Lociuro (3), M. Seymour (4), S. J. Warrington (2)
In this microdose (phase-0) study,the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection, were explored.
Four healthy men each received two single, 100 μg microdoses of 14C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of 14C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of 14C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS.
The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary.
A full copy of this paper can downloaded by following this link.
1. School of Pharmacy, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, UK
2. Hammersmith Medicines Research, Cumberland Avenue, Park Royal, London, NW10 7EW, United Kingdom
3. Via al Lido—Residenza Fortuna, 6817, Maroggia, Switzerland
4. Xceleron Inc., 20340 Seneca Meadows Parkway, Germantown, MD, 20876, USA
Xceleron are pleased to announce that accreditation for biobased testing under the European Standards CEN/TS 16137 and BS EN 15440 were received today. This accreditation is an expansion of our accreditation in the biobased field which also includes ASTM D6866 achieved earlier in the year.
Published: 9 April, 2013
Authors: David Higton, Xceleron Inc, Germantown, MD; Jenny Lin, Jim Yamashita, JCL Bioassay USA, Hoffman Estates, IL
Microdosing has been used as an investigative pharmacokinetic tool for approximately 10 years. Initial skepticism of the value of these studies was followed by investigative clinical trials to understand the circumstances when they provide useful data and this has led to routine use. When first introduced, accelerator mass spectrometry coupled with LC fractionation (LC+AMS) was the only technology that could provide the sensitivity required for these studies. Over the years, LC-MS/MS sensitivity has improved so that it is now viable to use this technique for microdosing studies, and a decision needs to be made on what technique to use.
To download a copy of this poster presented at the “7th Workshop on Recent Issues in Bioanalysis” (7th WRIB), please follow the link below.
New offering will expand access to powerful analytical platforms.
(Germantown, MD, USA; March 19, 2013) – Xceleron, a leader in the design and use of ultra-sensitive Accelerator Mass Spectrometry (AMS) in novel clinical investigations, has announced a partnership with JCL Bioassay, a leader in the use of highly sensitive LC-MS/MS and proprietary methodologies. The new partnership will offer drug developers access to the broadest range of sensitive and robust analytical platforms in early clinical development across Asia, Europe and N. America.
Phase 0 and enriched Phase 1 studies have been used successfully in recent years to investigate a range of developmental endpoints including drug presence at the tissue or cells of interest, absolute bioavailability and human metabolism. Investigations of this type conducted early in drug development allow confident critical decision-making that offers a very cost-effective alternative when compared to later stages of clinical development.
The partnership between Xceleron and JCL Bioassay will provide access to clinical design expertise and the most appropriate analytical platform for the purpose of early clinical investigation. Xceleron and JCL Bioassay have between them developed over 100 analytical methods for Phase 0 and enriched Phase 1 investigations and both companies have recently built, equipped and staffed laboratories specifically for the purpose of ultra-low level analyses under GLP and GCP conditions.
“This partnership emphasizes the critical role of contemporary analytical platforms in driving down the cost of drug development. Whether in Phase 0 or enriched Phase I, we can confidently provide critical PK and PD information before Phase II” said Dr Michael Butler, CEO of Xceleron.
“With 27 years’ experience in providing services for bioassay work coupled with-state-of-the-art analytical instruments, our researchers are well positioned to conduct ultrasensitive bioanalyses. This has led to the continuous growth of our company as a leader in the bioanalytical field and enables our customers to make rapid and precise decisions on their drug development programs. The partnership with Xceleron further expands the geographic and technological scope of the services we can provide to our customers and promotes the use of these cutting-edge analytical platforms to detect low level analytes in early drug development” said Jenny Lin, Vice President of Operations and CSO of JCL Bioassay USA, Inc.
Xceleron provides bioanalytical AMS services for accelerated early drug development. The company pioneered human microdose and microtracer techniques using ultra-sensitive AMS to investigate the pharmacokinetics and metabolism of developmental drugs in Phase 0, Phase I and Phase II/III clinical trials. It has been providing drug development services for more than 10 years and has conducted more GLP and GCP studies than any other analytical service provider of its type. Visit Xceleron at www.xceleron.com.
About JCL Bioassay
JCL Bioassay USA, located in Hoffman Estates, IL, is a leading Japanese CRO and a global provider specialized in Bioassay services in support of TK/PK studies for pre-clinical and clinical developments. The company provides cutting-edge capabilities and sophisticated expertise in Bioanalytical method development, method validation/qualification and study sample analysis for small and large molecules. The company also pioneered microdosing analysis in Japan. As a strategic drug development partner, JCL Bioassay USA helps sponsors to overcome challenges in Bioanalysis with expertise, rapid turn-around-time and high quality services. For more detailed information, visit JCL Bioassay USA at www.jclbiousa.com.
(Germantown, MD, USA; February 26, 2013) — Xceleron, a leader in the design and execution of novel clinical investigations using ultra-sensitive analytical technology, has announced a partnership with Kinetigen, a clinical pharmacology consulting firm specializing in pharmacokinetics. The partnership will offer drug developers simpler and more robust early clinical investigations.
Non-optimized or incomplete pharmacokinetic analyses commonly result in additional expenses and lost time over the course of a development program; such problems frequently become evident during expensive proof-of-concept investigations. Thoroughly understanding the pharmacokinetics of a drug or biologic in clinical Phase I studies allows investigators to make decisions earlier. Phase I pharmacokinetic investigations must be properly designed to ensure that their results will translate into proof-of-concept and must be conducted in a cost-effective manner.
(Germantown, MD, USA; January 31, 2013) — Xceleron, a leader in the application of ultrasensitive Accelerator Mass Spectrometry (AMS) to low-level quantitation of carbon isotopes, and Intertek, a global leader in providing quality and safety services to a wide range of industries, have entered into an agreement to help companies address their challenges in creating sustainable businesses. This agreement offers Intertek’s customers a solution for measuring renewable, bio-based content in carbon-based materials, such as fuels, packaging and other matrices. This will enable them to more easily meet and report on corporate sustainability and social responsibility goals.
A ‘bio-based product’ is a commercial or industrial product (other than food or feed) that is composed, in whole or in part, of biological products or renewable agricultural (plant, animal and marine) or forestry materials. The AMS technology at Xceleron accurately measures renewable carbon content and, as part of Intertek’s sustainability and social responsibility solutions, it will provide clients with a single source to assure their sustainability goals are met.
FDA drug approvals 2013: 5 out of 27 supported by AMS enabled studies
"...AMS [is] an invaluable tool in our early drug development program, allowing us to quickly assess bioavailability in humans and focus resources on our most promising drug candidates going forward."
Find out how we can help you accelerate your drug-development program.