SERVICES

Services deal with pharmaceuticals, polymerics, nutrition, medical devices, nutraceuticals, cosmetics, food ingredients, applied biochemistry and metabolism along with clinical medicine. Company efforts frequently involve analytical problem-solving related to environmental health, biomaterials, or forensic challenges. CAT also has special interests in establishing process design and manufacturing controls over high molecular weight, water-soluble products used in many foods and medicines.

While few analytical firms specialize on water soluble polymers—we do. Studies range from microbicides that retard AIDS virus transmission around the globe to polymeric humic acid structures that promote reforestation after the ravages of forest fires. Beyond this, we are responsible for pioneering the routine safety and surveillance analysis of intravenous nanoparticle drugs where problematic aggregates unexpectedly develop without warning. Exemplary product models of this behavior include iron nanoparticles used for iron replacement therapies in the course of chronic kidney dialysis treatments or certain cancer therapies.

CHROMA SERVICES

Multi-Angle Laser Light Scattering (MALLS)

Due to growing applications for high molecular weight aqueous polymers in the biopharma and medical device sectors, we specialize in LC methods using MALLS instrumentation from Wyatt Technology Corporation.

Structural characterizations for aqueous polymers have expanded because many innovative biotech products originate from natural products. Typical among these are starches, hyaluronic acid, pectin, carrageenan, collagen, chitin and others. Depending on the source, environmental growth conditions, and many other factors, naturally-based polymeric structures may have similar but significantly different molecular details that affect product development and function. Many of these critical differences can be detected by LC methods interfaced with MALLS detection either alone or in conjunction with other supporting methods.

By initially characterizing a raw polymer, future engineering or modification of the polymer will increase the likelihood of reproducibly making a desired product with a similar function. For example, antitumor features of pectins made from fruits in the US Gulf Coast region fail to mirror the same antitumor properties of pectins from Mediterranean regions. This occurs because the fundamental molecular structures of raw natural products are slightly different from one geographic region to another but they are both pectins.

For carbohydrates, proteins, and nanoparticles, the use of MALLS as a LC detection method has advantages over other detection methods. This has relevance for specialized (1) development, (2) manufacturing, (3) stability (i.e., shelf-life), or (4) degradation studies involving large aqueous molecules and assemblies. Such studies are critical wherever biologically and pharmaceutically active aqueous polymers are used because their structural integrity is related to their safety or function and sometimes both.

Moreover, verifying the presence of key molecular properties supporting objectives 1–4 above are frequent prerequisites to the regulatory approval steps for pharmaceuticals. Beyond this, structural characterizations for products give a possible forewarning of adverse events or functional product failures before they happen. Not to be outdone, food science and technology as well as material science specifications for many products get valuable performance insights into their products too by way of LC-MALLS results.

In the case of traditional LC applications, the detection and quantification of analytes was considered to be a satisfactory analytical outcome. For example, analytical goals may have focused on estimating the molecular weight of an analyte or detecting its mass. Now however, the molecular structures of pharmaceutically tolerated or biomedically-functional analytes require more defined analytical profiles.

While earlier analytical data such as molecular weight (Mw) or concentration may still be important, information about the size of a molecule and its molar mass are often required. Here, the size measurement viewed as the root mean square (R.M.S.) radius, or sometimes called the “radius of gyration,” has many useful implications. The R.M.S. radius is a measure of a molecule’s size weighted by the mass distribution about its center of mass. Once a molecule’s conformation is determined, its shape as a random coil, sphere, or rod can be related to its geometric dimensions in nanometers (nm). Beyond this, it’s often important to know the polydispersity of a polymeric analyte for steps in the regulatory approval process. Moreover, it can be critical to document the occurrence percentage of polymeric molecular weights that are say ″ 50 kilodalton (KD), ″ 100 KD or ″ 250 KD, These distinctions are useful to document below a specified Mw limit since low Mw fragments from starches as an example, may elicit adverse effect indications such as itching or mild erythma.

The realization that molecular shapes are related to molecular functions stems from the early structural studies of proteins originating with Anfinsen in the 1970s. But now, that concept has practical relevance to many other areas of molecular structure, architecture, and biotechnology.

For example, preferred carbohydrate and protein functions are dependent upon their unique shapes and conformations under physiological conditions. These functional molecular shapes reflect favored structural thermodynamic interactions at the molecular level. Thus, the unique native 3-dimensional (3-D) structure shown by similar molecules will affect their native biochemical functions—their structures being stabilized by hydrophobic, electrostatic, hydrogen bond, and substituent side-chain interactions to give a predisposed native molecular shape. Conversely, all other molecules of the same shape and structure will display a similar function.

The requirements for analytical biochemistry today are linked to the functional chemistry of molecules held within the 3-D spatial reaction matrix of living cells and tissues where they occur. Accordingly, the use of LC interfaced with MALLS makes good analytical sense because the function, performance, and molecular architecture of analytically important molecules will operate under similar spatial constraints and conditions related to analytical study.

Perhaps it’s time to consider the merits of LC interfaced with MALLS to solve your aqueous polymeric development challenges, or else adopt it in the context of a validated analytical testing program to get the most from your analytical budget and program. You will be glad you did.

Other Analytical LC-MALLS Services

Analytical services typically focus on biopolymers, material science, nutrition, medical devices, bio-/food technology, metabolism, and clinical medicine along with analytical problem-solving in environmental health and forensic areas. In some cases, analytical methods fulfilling client demands fail to exist. Then CAT scientists focus on designing and implementing new solutions for unique problems with a spirit of creativity in contract or service work.

Frequent analytical jobs focus on material identification, quantification or qualification, deformulation, patent infringement work, and “good” vs. “bad” characterization studies.

Beyond these areas, CAT focuses on biochemical engineering and process design controls to enhance the uniform manufacture of high molecular weight pharmaceuticals and nanoparticles. In many cases, the USFDA demands analytical characterizations for pharmaceuticals and large molecules at each unit step in their manufacture. This is often routinely achieved best by the specialized analytical chromatography and the expertise that we provide.