Recently IsoSciences has focused on the manufacture and development of complete syntheses of numerous marine toxins including gonyautoxin (CAS 60508-89-6 ; 60537-65-7, tetrodotoxin (CAS 4368-28-9) and saxitoxin (CAS 35523-89-8), along with related derivatives. Availability of stable isotope labeled versions of these toxins is critical for the development of analytical and diagnostic assays by LC/MS.
To assist studies that focus on the presence of these toxins in our food chain IsoSciences has developed stable isotope labeled derivatives in certified solutions (CertiMass) as well as solid form in order to create extremely sensitive mass spectrometric analysis tools. Both stable-isotope labeled and non-labeled saxitoxin derivatives are available to support these studies.
IsoSciences interest in developing molecules of this nature stems from the increasing interest in the multitude of natural product chemistries found in ocean plant and animal life. These sources provide compounds with a lot of potential for disease prevention. In addition, the sometimes lead to cures and, not uncommonly, may be in the form of a toxin. A great example of this is Gonyautoxin. At certain doses this algae-produced toxin is lethal, yet when used at extremely low doses can be used to heal certain medical conditions.
The potential reward associated with marine biochemistries has led to a surge in the study of various aspects of shellfish byproduct, fish and mammal skins/cells and relevant ocean fauna. However, in recent times a lot of concern has been raised over the presence of specific toxins in shellfish that finds its way into mainstream food supplies and can ultimately cause sickness within the human population. One particular example of this was the large scale mortality of Hump Back Whales that initially was blamed on pollution in the late 1980's. After further investigation and major poisonings of human population it was determined that the root cause was not directly pollution, but a set of algae-based biotoxins - the most famous, and likely significant, member being Saxitoxin. The shellfish that consumed the Saxitoxin-rich algae would ultimately concentrate the toxin within its edible structure and when consumed would cause potentially lethal poisoning of the consumer. Often times these algae will suddenly bloom in nutrient rich coastal waters resulting in infamous “Red Tides”.
In the left figure we have outlined a nitrogen-15 labeled derivative of saxitoxin that would represent four additional mass units versus the unlabeled form. This 15N4 labeled standard will allow for exact quantification of saxitoxin levels by mass spectrometry. This newly available labeled standard will allow for the most sensitive and accurate analytical assay available.
If your studies or interests require the use of these, or related, toxins please contact the IsoSciences staff. We may already have the labeled toxin available in our synthetic database and catalog, else we can discuss how the IsoSciences chemists we can work with your team to custom synthesize a new material.
Saxitoxin | Gonyautoxin | Marine Toxins
As disease and health analyses progress, the desire to monitor and analyse simpler chemical and biochemical structures has also increased. Studies have moved from the human genome to the transcriptome to the proteome until more recently the focus has been squarely on the metabolome. The human metabolome is studied with an eye to studying the small chemical fingerprints that are left behind from cellular and related processes. As such the types of molecules usually studied are sugars, lipids, amino acids, peptides and other small molecules. These biochemistries are reviewed and are effectively utilized as biomarkers that can help determine a specific disease or potential disease state that could exist within a cell and patient.
Given the very low metabolome chemical concentration, analysis techniques have to be very sensitive in order to confidentally monitor the metabolome. Advances in mass spectrometry coupled with the availability of stable isotope labelled derivatives at IsoSciences allows the detailed analysis necessary in order to create reliable metabolomic and biomarker methodologies for the potential diagnosis of relevant disease states.
IsoSciences' synthesis team has created a broad catalog of readily available metabolomic relevant molecules including hormones, steroids, bile acids, amino acids and other relevant small molecules. All available molecules can be ordered online. However, if you need a specific metabolomic molecule that is not present in our catalog, please feel free to contact us by email or phone in order to discuss how we can assist with a custom synthesis to supply your needs. IsoSciences has a very high success rate with custom synthetic needs and our chemists have frequently been critical in generating the best possible standards for new customer application needs.
All metabolomic chemistries currently synthesized by IsoSciences catalog can be found here.
Metabolomics | Metabolomic
IsoSciences has continued to expand its offering of Vitamin D standards. We have the most complete offering of Vitamin D derivatives on the market and, importantly, IsoSciences is the source manufacturer of all of them.
Some of our vitamin D derivatives are unique to IsoSciences. For example, we are working on a number of 13C labeled vitamin D derivatives for critical applications where deuterium may be problematic. While some molecules, like the side chain labeled 2H6 derivatives, have been on the market for some time and are perfectly suitable for some applications. Our goal is to make all of the options available to you at one location, in one catalog. While stable isotope labeled Vitamin D standards were pioneered by IsoSciences we continue to believe we can earn your business by understanding your application needs and offering the most efficient technical solutions, coupled with the highest quality product.
The new Vitamin D3 derivatives that are currently in stock and available include:
- 24R,25-Dihydroxy Vitamin D3 Unlabeled
- 25-Hydroxy Vitamin D3-[26,26,26,27,27,27-2H6]
- 24R,25-Dihydroxy Vitamin D3-[26,26,26,27,27,27- 2H6]
- Vitamin D3-[23,24,25,26,27-13C5]
- CertiMass Catalog #S13036-0.1
- Vitamin D3-[25,26,27-13C3]
- CertiMass Catalog #S12334-0.1
The new labeled vitamin standards that are being completed and will be available soon include:
- Vitamin D3-[26,26,26,27,27,27-2H6]
- 25-Hydroxy Vitamin D3-[23,24,25,26,27-13C5]
Please contact us via email or phone if you wish to preorder the soon to be completed materials, or simply wish to discuss a specific need you have. IsoSciences has a very high success rate with custom synthetic needs and our chemists have frequently been critical in generating the best possible standards for new customer application needs.
All other vitamins synthesized by IsoSciences catalog can be found here.
Improved Vitamin D Standards
Isotope analysis has been broadly used in the scientific community for several decades. The advancement of mass spectroscopy techniques has allowed users to determine isotopic fingerprints for natural and synthetic materials. This methodology has been extended to pharmaceutical developers and manufacturers to determine the metabolic degradation of the API, but also to authenticate end-manufactured drug APIs and ingredients.
IsoSciences specializes in the synthesis of organic molecules and molecules of biological interest. Starting with typical organic and labeled raw materials, the synthetic chemists at IsoSciences are able to create successful paths to labeled precursors, labeled intermediates, labeled APIs and finally, labeled drugs and metabolites, while incorporating the stable isotope label in strategic locations. The location of labels is critical to creating a molecule that ultimately gives the information necessary during the metabolic processes.
Additionally, it has been found in recent work that strategic incorporation of stable isotope labeled APIs can ultimately allow an improved technical performance. For instance, careful replacement of hydrogen with deuterium could potentially lead to increased bioavailability in addition to the inhibition of biological processes that could lead to toxicity and other related side effects. The synthesis of labeled APIs has many potential benefits from monitoring the authenticity of the drugs, determining the metabolic decomposition of the labeled active ingredient, and potentially the development of new APIs by improving technical performance of non-labeled APIs.
Strategic development of a labeled API is very important and so is selecting a veteran team that can help develope suitable APIs for a metabolic study. For example, if an API study of Rifampicin (see structure) was necessary the IsoSciences team would consider all reasonable metabolic break points (e.g., hydrolysis of ester or imine functionalities, or oxidation of the para-dihydroxynaphthyl structure) and then determine where best to place stable isotope labels in order to synthesize a suitable labeled candidate.
Come visit IsoSciences at MSACL 2013! (If you can’t make it, that’s OK you can see the banner above and please feel free to contact us with any questions you may have.)
IsoSciences is a world leader in the synthesis of labeled molecules of organic and biological interest. Our team of PhD synthetic chemists has over 100 years of experience developing and executing synthetic routes to stable isotope labeled molecules and intermediates. With a catalog that is constantly expanding to stay on the forefront of pharmaceutical and diagnostic analysis needs, IsoSciences is also renowned for developing custom synthesis solutions for specific targets and APIs.
Some of our recent advances and topics of interest -
- Improved assay quality and accuracy with new 13C diagnostic standards
- Enhanced Aldosterone analysis and stability with Aldosterone-d4
- Discuss the recent 29 step synthesis of labeled Saxitoxin – a world first!
- A more stable dihydrotestosterone, utilizing 13C labeling
- Review the broad classes of standards synthesized and readily available in our catalog
- Custom synthesis capabilities
- Certified solutions of analytical standards
- Custom CertiMassTM solutions for your analytical needs
To understand how our D, 13C, 15N and 18O labeling capabilities may assist your needs, please come visit us at our booth at MSACL 2013. While you are there pick up your free USB memory stick (it is no ordinary thumb drive, so don’t get there too late, they will be snapped up quickly!)
Not all stable labeled Aldosterone molecules are the same!
Aldosterone is a steroid hormone secreted by the adrenal cortex that is implicated in hypertension, hyperaldosteronism (Conn syndrome and secondary hyperaldosteronism) and adrenal insufficiency (Addison's disease). Tests for aldosterone by mass spectroscopy are one of the most common steroid mass spectroscopy studies performed.
IsoSciences was the first to develop the deuterated mass spectroscopy standard aldosterone-[2,2,4,6,6,17,21,21-D7]. Now we have developed a new labeled form of aldosterone, aldosterone-[9,11,12,12-D4] , that places all the deuterium labels in completely non-exchangeable positions. Both standards are available from IsoSciences for these critical mass spec assays.
Aldosterone-[D4] is available in two forms - as a solid (catalog #: 11214) and as an exact concentration CertiMass™ solution: (catalog#: S11214). Aldosterone-[D7] is also available in two forms - as a solid (catalog #:5093) and as an exact concentration CertiMass™ solution: (catalog#: S5093)