An Introduction to Dissolution Testing and Development
Dissolution testing is the monitoring of drug substances in a controlled environment from a solid dosage form (i.e., capsules, tablets) to a solution state. These “tests to characterize the dissolution behavior of the dosage form, …also take disintegration characteristics into consideration, are usually conducted using methods and apparatus that have been standardized virtually worldwide over the past decade or so, as part of the ongoing effort to harmonize pharmaceutical manufacturing and quality control on a global basis.”1
Devising a Strategy When devising a dissolution testing strategy, “a simple but broadly applicable analytical method is always desired.”2 Dissolution analysis is generally performed via UHPLC for faster sample analysis due to thenumber of samples required. Creating an analytical method should incorporate guidelines from The European Medicines Agency’s (EMA) International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which are also interchangeable with the FDA. These are designed to “avoid redundant testing by (the) industry.”3
It’sthe Media… Dissolution testing is designed to mimic conditions found in the human stomach. As these conditions vary widely from patient to patient, so too should the testing environment. The ranges for the media should allow for various pH levels. These sets should be notated and designed to simulate FaSSGF (fasted state simulated gastric fluid), FeSSIF (fed state simulated intestinal fluid), and FaSSIF (fasted state simulated intestinal fluid). Compendial media is generally HCl or sometimes acetate or phosphate pharmacopeial buffers. As mentioned, with this many simulated environments, along with multiple time sets/points, there will be many samples necessary, and analysis by UHPLC is optimal for timely turnarounds.
We Can Assist with your Dissolution Testing and Development Needs
AMPAC Analytical has years of experience and numerous experts in dissolution testing. We can support release testing, stability, method development, and assist with formulation development through dissolution analysis. We utilize paddle and basket apparatuses in the dissolution phase of testing.Additionally, our equipment offerings include Agilent Infinity II and Thermo Fisher Vanquish Horizon UHPLCs. Please contact us with any specific questions or to receive a quote for your drug product dissolution testing and developmentneeds.
(Per- and) PolyFluoroAlkyl Substances (PFAS) are a class of ubiquitous chemicals that have been found in water, air, fish, and soil across the nation and worldwide. Known as “Forever Chemicals,” there are thousands of different PFAS, and they are present in consumer, commercial, and industrial products.1 Having one of the strongest bonds in organic chemistry, their structures proved to be resistant to heat, water, oil, and degradation.2 They are found in “food packaging and non-stick cookware, cosmetics, waterproof and stain-proof textiles and carpet, aqueous film forming foam (AFFF) to fight Class B fires, and as part of metal plating processes.”3 Teflon and Scotchgard were two of the pioneering products to utilize these fluoropolymers. The two most common PFAS are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS).
Health Concerns of PFAS
Some of the most frequently cited health concerns associated with PFAS include adverse cardiovascular, immunity, developmental, and hepatic effects.3,4The most commonly heard refrain to minimize these concerns is that if they are so prevalent, why are there
not more health issues associated with them? In fact, “The Lancet Commission on Pollution and Health reported that pollution was responsible for 9 million premature deaths in 2015, making it the world’s largest environmental risk factor for disease and
premature death.” This was updated in 2019, and those numbers held steady, accounting for one in six deaths worldwide.5/i> While this number includes all types of pollution, the impacts are clear.
The Exposure Concerns of PFAS Are Regulatory and Legal
Due to their combination of persistence, pervasiveness, mobility, and the ability of some to bioaccumulate (or build up in animals and humans), they have been in the news recently too.6 Predictably, they are also now moving through the courts.7-9 Some of the most common areas of litigation are directed at PFAS found in drinking water and firefighting foam. The regulatory initiatives are also increasing. These address a range from water and soil to numerous manmade products including food packaging.10,11 The European Chemicals Agency (ECHA) and the NIH have a wealth of guidance and regulations that apply to PFAS.12,13
The EPA has useful direction for analytical methods development and sampling research that outlines the “laboratory validation process following a particular rulemaking or guidance effort and are available to support regulatory or guidance activities.”14 For
technique and equipment, PFAS are typically analyzed by mass spectrometry, coupled with gas chromatography or liquid chromatography (GCMS and LCMS), which enables detection in the low parts per billion.
AMPAC Analytical has years of experience and numerous experts in trace analysis by mass spectrometry who can assist with method development for high-volume analyses for both common and atypical sample matrices that will allow you to stay ahead of evolving regulatory concerns. Please contact us with specific questions or to receive a quote for PFAS quantitation.
Background on Chiral Purity Chirality refers to the phenomenon that occurs when a mirror image cannot be superimposed. It is sometimes called “optical rotation”.
The origin is from the late 19th-century Greek word kheir (‘hand’) and is one of the easiest demonstrations of the concept. Although a person’s hands may appear virtually identical, if they were switched, the outcome would be very different. Amino acids and sugars are the chiral building blocks of larger molecules such as peptides, proteins, and nucleic acids. Therefore, those polymers, in turn, are chiral as well.1Molecules with chiral centers may have a different therapeutic impact, and this guides the need to test and control chiral purity. The effects of chiral impurities can result in horrific outcomes, as evidenced by the infamous birth defects associated with Thalidomide2 or as benign as Aspartame and sugars (the D/L sugars) that, when superimposed, can create different taste sensations (sweet versus sour, etc.) or metabolic activity. Each chiral center can generate two enantiomers. “Enantiomers or optical isomers are chiral molecules which are non-superimposable mirror images of each other,”3 and multiple chiral centers can generate diastereomers (non-mirror image isomers).
Determining Purity HPLC has been the primary technique for determining chiral purity, with gas chromatography used occasionally. Measurement of optical rotation is a legacy technique that is fast but not as accurate. Historically, HPLC methods used under normal phase conditions could limit the type of molecules that could be analyzed. However, now modern chiral columns are compatible with reverse phase conditions.
Simulated Moving Bed (SMB) Chromatography as an Option for Chiral Purity Analysis Do you have a partner for chiral separations? AMPAC Analytical has the expertise in performing chiral purity testing, along with the equipment and techniques. Additionally, our parent company, AMPAC Fine Chemicals, has decades of experience conducting chromatographic separations at a commercial scale in a highly regulated environment. Our services include SMB screening, method development, proof-of-concept demonstration, and production. We operate the largest CGMP Simulated Moving Bed (SMB) chromatography unit in the United States. These technologies and expertise are part of a one-stop shop (from 10-millimeter columns up to 1000mm). Our SMB processes can be developed in a few weeks and are easily scalable. In many cases, scale-up from gram to multi-ton quantities can be achieved in fewer than six months. Our facilities include kilo-scale and pilot-scale units to support smaller quantities, also under CGMP conditions. The SMB facilities have been inspected and approved by the FDA for the manufacturing of APIs. AFC has registered four products with regulatory authorities (FDA/EMA) using SMB technology. Along with chiral separations, we can also perform the separation of diastereomers & regioisomers.
Contact us today for information on how we can assist with your raw material, amino acid, drug product, and API chiral purity testing or to learn more about our SMB processes.
The linkage between nitrosamines and cancer was first postulated by William Lijinsky in 1970. Then, in 2018, N-nitroso-dimethylamine (NDMA)) was detected in an active pharmaceutical ingredient, Valsartan (an Angiotensin-II-receptor antagonist). Finally, the FDA issued a guidance for the industry, “Control of Nitrosamine Impurities in Human Drugs”, in the fall of 2020. However, the guidelines continue to evolve. There has been an update in March of 2021, with ongoing risk assessments. Other regulatory agencies have instituted their own, along with updates. For example, since our blog series on nitrosamines, there have been some regulatory updates from the European Medicines Agency (EMA). Their new guidelines are outlined in a document entitled, “Questions and Answers for Marketing Authorization Holders/Applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 Referral on Nitrosamine Impurities in Human Medicinal Products.”1 The updated section answers the crucial question, “Which limits apply for nitrosamines in medicinal products?”
The answers are provided with a definition of nitrosamines and acceptable exposures:
“The ICH M7(R1) guideline defines N-nitrosamines as substances of the “cohort of concern” for which limits in medicinal products refer to the so-called substance-specific acceptable intake (AI) (the Threshold of Toxicological Concern, TTC, value of 1.5 ug/day cannot be routinely applied) which is associated with a negligible risk (theoretical excess cancer risk of <1 in 100,000 over a lifetime of exposure). The calculation of AI assumes a lifelong daily administration of the maximum daily dose of the medicinal product and is based on the approach outlined in the ICH M7(R1) guideline as well as the principles described in relation to the toxicological evaluation in the assessment report of the CHMP’s Article 5(3) opinion on nitrosamine impurities in human medicinal products.”1,2 (A previous blog examined TTC, here.)
A Useful List of Nitrosamine Limits
In Appendix 1 found on the EMA site, there is a list of more than eighty nitrosamines listed, along with CAS numbers, known medicinal sources, CPCA (Carcinogenic Potency Categorization Approach) categories, and their guidance publication dates.3,4
There are some exceptions that should be considered. For example, the EMA states, “The ‘less than lifetime’ (LTL) approach should not be applied in calculating the limits as described above but can only be considered after consultation with competent authorities as a temporary measure until further measures can be implemented to reduce the contaminant at or below the limits defined above.”1
Additionally, those medications intended for advanced cancers also have some exceptions. For example, “If the active substance itself is mutagenic or clastogenic at therapeutic concentrations, N-nitrosamine impurities should be controlled at limits for non-mutagenic impurities according to ICH M7(R1).”
There is also guidance when one or more than one nitrosamines may be present. For the latter, the guidance advises one of two approaches:
The total daily intake of all identified N-nitrosamines is not to exceed the AI of the most potent N-nitrosamine identified.
The total risk level calculated for all identified N-nitrosamines is not to exceed 1 in 100,000. The approach chosen needs to be duly justified by the MAH (Marketing Authorization Holder)/Applicant.1
Final Thoughts on Nitrosamines
Nitrosamine guidance worldwide is ever-evolving, yet the impetus to quantify and regulate them is clear. There will doubtlessly be further updates to regulations. AMPAC Analytical Laboratories – an SK pharmteco company (AAL) is an industry leader in the detection of nitrosamines and other genotoxic impurities (GTI), We have the specialized expertise, equipment, and methodologies to detect these impurities by gas chromatography or high-performance liquid chromatography coupled with mass spectrometry to support your API project. Also, importantly, AAL can assist in navigating those projects within today’s regulatory landscape. Please contact us with any specific questions or to receive a quote for nitrosamines or other GTIs.
Dynamic Vapor Sorption (DVS) is a gravimetric technique used to measure the change in mass of a material in response to changes to surrounding conditions such as temperature or humidity. DVS is primarily used with water vapor but can be applied to other organic solvents as well for the physicochemical characterization of solids.
DVS was developed by Daryl Williams, the founder of Surface Measurement Systems Ltd., in 1991. The company then delivered the first working DVS instrument to Pfizer in 1992.1 Since then, many other equipment manufacturers have entered the field.
Figure 1: A DVS isotherm plot indicating sorption and desorption rates and hysteresis. The isotherm shows a typical hysteresis curve where the adsorption phase is almost identical to the desorption phase (i.e. reversible). Note that at 80 %RH, there is net sorption of 0.9% between adsorption and desorption traces. The material appears to be slightly hygroscopic according to the definition in Ph. Eur.2
Sorption, Desorption, Absorption, and Adsorption There are five main physical processes that occur during the DVS experiment. The first, sorption, is when a material takes on moisture due to increased humidity. Conversely, desorption is the process that occurs when the material loses moisture due to decreasing humidity. Sorption can be classified as one of two types. Adsorption is moisture that is observed on a surface of a material, while absorption is moisture that has penetrated the surface of a material. The fifth term and the term that relates sorption and desorption is called hysteresis. The overall chart that includes and tracks the sorption and desorption rates and hysteresis is called the isotherm. These curves are crucial for understanding the physicochemical characteristics of a solid, such as porosity, polymorphic change, or liquefying of a sample.2
There are numerous reasons to utilize DVS, and some of the most common within the active pharmaceutical ingredient (API) industry are:
To determine the sorption isotherm;
To evaluate the hygroscopicity of an API powder;
To compare the hygroscopicity of different solid-state forms: solvates, polymorphs, salts, amorphicity, and cocrystals;
To determine the deliquescence point of a material;
To quantify and qualify the amorphous content in drug substance orexcipient,3 and
To evaluate packaging materials.
Of course, there are a variety of other applications in other industries, including for building materials, food science, cosmetics, coatings, and sealants.
DVS Analysis of APIs For pharmaceutical development, DVS is used for a variety of applications, including screening early drug and excipient candidates, establishing processing parameters, and identifying packaging and storage requirements (Figure 2).4,5
Figure 2: A DVS isotherm of an API showing that the material started to gain significant mass after exposure to relative humidity values of more than 60 %RH. The change here was irreversible, as demonstrated by the desorption curve. DVS could be a useful tool to suggest storage conditions in terms of humidity contents in the surrounding environment.
However, due “to the typically slow establishment of an equilibrium, DVS experiments are rather time-consuming.”4 Nevertheless, “water content of solid active pharmaceutical ingredients and excipients, individually and when formulated in pharmaceutical dosage forms, is a parameter that should be monitored throughout the drug lifecycle.”5
As an analytical technique for APIs, DVS has become a necessary step within drug development and production, reducing issues that can arise during manufacturing, packaging, transportation, solubility, dissolution rate, stability, or storage. AMPAC Analytical’s sister company, SK biotek Ireland Analytical Services, has the experience, technology (including a Surface Measurement System’s DVS Resolution Dual Vapor Gravimetric Sorption Analyser), and support, to assist with this vital testing. Both companies are part of SK pharmteco and can easily transfer your project from either business unit to ensure the most optimal solution and logistical support are provided to meet your product timeline. We invite you to contact our team members and discuss how we can assist with your sorption testing requirements.
Figure 3: A SMS DVS instrument like the one located at SK biotek Ireland.
Effective method development is crucial for the quality control of Active Pharmaceutical Ingredients (API) and Drug Products (DP). Thorough method development enables successful downstream method validation.
The regulatory guidance specifies that:
Method development and validation vary by application (quantitative, qualitative, etc.).
It is phase appropriate.
The client may provide additional guidance/validation criteria.
The validation guidance directs how AMD (analytical method development) is conducted.
Early Adoption of Forced Degradation Analysis It is recommended that forced degradation be performed early in the method development lifecycle and that method parameters are suitable for mass spectrometry. This will prevent many issues that could occur in later stages and ensures the primary purity method is stability-indicating (specificity). When performing forced degradation, these considerations should be weighed:
Always utilize a control sample without exposure to stressors.
The stressors generally consist of acid, base, peroxide, heat, and photolytic conditions. Other stressors may be used based on known material incompatibility
After exposing the compound to these stressors, target 5-20% degradation of the main peak.
If degradation is not observed under reasonable conditions, then the material can be considered stable under those conditions.
Impurity Genesis and Identification Assessment Acceptance criteria should be scaled to impurity levels. How can the method unequivocally assess the analyte of interest in the presence of likely impurities, degradants, and the sample matrix? Additional considerations include:
Is themethod capable of identifying and/or quantifying a specific compound?
Are there solvents present that can interfere with potential impurities?
Known impurities? Are the known impurities stable under the method conditions?
Is the method specific for degradation byproducts for stability-indicating methods?
Cross-Platform Method Robustness Robustness refers to a method’s ability to meet its analytical requirements (system suitability requirements) despite small variations of the method’s parameters, such as discrete changes to a column or sample tray temperature, percent organic modifier, flow rate, and detector wavelength. This capability is typically built into the method during method development.
Precision or Accuracy – You Need Both in Strong AMD AMPAC Analytical development strategy involves the early adoption of forced degradation studies with the goal of every primary purity method being stability-indicating (specificity) and mass spectrometry compatible. The validation strategy is phase-appropriate and application-specific and guides the development strategy. The validation acceptance criteria guidelines are specific to the test methodology, intended use, and level. Finally, method lifecycle performance is assessed, and reevaluation or revalidation can occur.
Contact us today to learn how we can create accurate, precise method development for your API and DP pipeline.
The Cost of Drug Discovery and Development and How to Mitigate It
The path to successful drug discovery and development is extremely long, expensive, and risky and can take between 10 to 15 years at an average cost of more than $1–2 billion for every new drug that is approved for clinical use.1,2 In fact, preclinical drug discovery alone “typically takes five and a half years and accounts for about one-third of the cost of drug development.”3,4 Therefore, even during the earliest stages of a drug product or active pharmaceutical ingredient project, phase-appropriate method development should be instituted to manage costs. This bolsters the chances for success and ensures reliable results, quality management, and reproducibility while avoiding “unreliable results (that) might not only be contested in court but could also lead to unjustified legal consequences for the defendant or to wrong treatment of the patient.”5 At its most basic, phase-appropriate method development maps the “what is needed” to “when it is needed.”6 Effective phase-appropriate method development can provide long-term product support by introducing mass spectrometry compatibility and forced degradation development to ensure your methods are stability-indicating and amenable to unknown impurity identification. By instituting a phase-appropriate method development process, combined with a quality-by-design approacharound each logical sequence of events – and rigorously following it – it is more likely to create a cost-effective, successful outcome as you take the drug product through the regulatory process.
It Can Pay to Outsource
As the incentives for strong phase-appropriate method development increase, so too has the recognition of its value. Unfortunately, “it is not uncommon…to find pharmaceutical companies and contract research organizations (CROs) that are not taking advantage of the phase-appropriate approach and simply reference the typical ICH guidance for analytical items, such as method validation.”7 However, while FDA guidance encourages the use of a phase-appropriate approach, it is lacking in details and requirements. This leaves many companies to seek out ICH guidance as an alternative, conservative approach. Also, within their CGMP quality system, they may find it difficult to accommodate differing levels of CGMP compliance throughout the various clinical phases of development. This is when it might be an opportune moment to consider an outside expert that specializes in phase-appropriate method development processes for drug discovery and validation. A successful yet robust phase-appropriate method development program can balance competing interests and requirements and still provide a regimen that meets the overall development goals without sacrificing any of the requirements of the program.
AMPAC Analytical Laboratories (AAL), an SK pharmteco company, has decades of experience in providing a wide array of release testing services for raw materials, intermediates, APIs, and drug products. Our labs are equipped to handle hazardous, cytotoxic/high potency compounds as well as controlled substances for schedule II through V. Additionally, we have not only the expertise to conduct forced degradation experimentsbut also appropriate instrumentation like mass spectrometers to support later phases of development for your products. Please contact us to discuss how we can ensure the success of your drug discovery and development project and simultaneously reduce risks.
“The dose makes the poison” – Paracelsus (c. 1493– 1541), born Theophrastus von Hohenheim
The Threshold of Toxicological Concern (TTC) refers to levels of mutagenic impurities expected to pose a negligible carcinogenic risk.1 The US FDA, the EMA (European Medicines Agency), and the European Food Safety Authority (EFSA) all have TTC values and regulations in place for food and active pharmaceutical ingredients (APIs), along with numerous other products.2,3 Originally, these standards were applied to TTC levels from oral ingestion but have expanded to even include cosmetics and fragrances.4,5
One tool to assess risk is the use of Cramer classes for organic impurities. They range from I-III, indicating a low, medium, or high probability of toxicity.5
There are numerous tools and techniques to assess TTC, depending on the product (food, water, and other beverages, APIs, or cosmetics) and the mutagenic impurity. AMPAC Analytical can utilize TTC guidelines and risk assessments to establish method development and validation targets that ensure acceptable levels of mutagenic impurities in your API or food products. Contact us today to learn more about analytical strategies to control mutagenic impurities.
Forced Degradation is an important addendum to our previous post on Stability and Storage. Stressors are applied to new APIs and drug products to determine their degradation pathways and products under a variety of environmental conditions, including acid, base, light, heat, and oxidation. Forced degradation studies are also known as stress testing, stress studies, stress decomposition studies, and forced decomposition studies. These conditions “…are more severe than accelerated (stability) conditions and thus generate degradation products that can be studied to determine the stability of the molecule.”1
Regulatory requirements for forced degradation were enacted by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in 1993.2 However, these guidelines “are very general in (the) conduct of forced degradation and do not provide details about the practical approach towards stress testing. Although forced degradation studies are a regulatory requirement and scientific necessity during drug development, it is not considered as a requirement for (a) formal stability program.”1 However, stability studies have become a requisite for new drug moieties. In the absence of specific guidelines, the amount of stress needs to be representational: “Overstressing a molecule can lead to degradation profiles that are not representative of real storage conditions and perhaps not relevant to method development. Therefore, stress-testing conditions should be realistic and not excessive.”3
AMPAC Analytical (AAL), an SK pharmteco company, can assist with forced degradation studies for products at all phases of development, in tandem with stability, storage, and method development, to ensure the viability of the drug products as they were designed. We introduce forced degradation studies early in method development to ensure your product quality throughout the development lifecycle. Contact AAL today to learn more.
The Background, Advantages of, and Considerations for Radiolabeled Peptides The use of radiolabeled peptides is a well-established tool in researching and treating many diseases and conditions. Selective receptor-targeting peptides are utilized as agents due to their rapid circulatory and tissue clearance and the high affinity and specificity to their targets. Peptides also have a relatively small size and low molecular weight compared to proteins and antibodies. There have been innovations and improvements in the design of peptides that incorporate chemical modifications with “impressive diagnostic accuracy and sensitivity.”1 Coupling these peptides with radiolabeling for peptide receptor radionuclide imaging (PRRI) and therapy (PRRT) has yielded remarkable results. In fact, a historical summary of radiolabeled peptides asserts, “The emergence of radiolabeled peptides for use with PET/CT such as 68Ga, 18F, and 64Cu, and the use of new receptor binding ligands…, have revolutionized PRRI and improved its diagnostic power beyond expectation.”2
“Criteria for a successful peptide tracer,” to be utilized for PRRI, “are a high target specificity, a high binding affinity, long metabolic stability, and a high target-to-background ratio.”3
Oncology and Radiolabeled Peptides Oncology has benefited from the “tumor-philic” properties of Arg-Gly-Asp (RGD) peptides “because of their high affinity and selectivity for integrin αvβ3 – one of the most extensively examined targets of angiogenesis. Since the level of integrin αvβ3 expression has been established as a surrogate marker of angiogenic activity, imaging αvβ3 expression can potentially be used as an early indicator of the effectiveness of antiangiogenic therapy at the molecular level.”4 In addition to integrin αvβ3 expression, “tumor angiogenesis…has been well recognized as an essential hallmark for tumor growth, invasion, and metastasis.”4 All this has made RGD-containing peptides “promising molecular agents for imaging angiogenesis.”5
Beyond Oncology Since integrins are “involved in adhesion between cells and the extracellular matrix” and, as such, are associated with normal and pathological states, this family of receptors is useful for targeting a range of diseases.6 Current applications include “cardiovascular imaging, atherosclerosis imaging, remodeling after myocardial infarct or stroke, imaging of myocardial ischemia, identification of abdominal aortic aneurysm, imaging of chronic inflammation, pulmonary inflammation, assistance with bone marrow evaluations, and tissue engineering.”6
A Brief History of RGD Peptides and Radiolabeling Although radiopharmaceutical therapies, which can concurrently detect and treat tumors (i.e., theranostics, a portmanteau of therapeutics and diagnostics), have been around for eighty years, it was not until the combination of these payloads was combined with peptides that the potential for better targeting became a reality. The use of the RGD peptide sequence to attach to cells was first reported by M.D. Pierschbacher and E. Ruoslahti in Nature, nearly forty years ago in 1984, as a feature of fibronectin.5,7 Next, targeting tumors with radioactive peptides began, initiated by OctreoScan’s breakthrough in the early 1990s, wherein somatostatin receptor subtype 2 (SST-2) positive tumors were identified.8,9 After that, the first monomeric integrin-specific PET tracer used in patients was F-Galacto-RGD, a glycosylated RGD-peptide.5,10 Since then, the tripeptide R-G-D sequence has generally been utilized as a tracer, carrying the isotope to integrins that are expressed on both tumor cells and activated endothelial cells of tumor neo-vasculature. In the ensuing years, advancements have continued apace, and going forward, the intersection of PRRI/PRRT from radiolabeled peptides combined with AI, precision, and personalized medicine assures transformative innovations.
Obstacles and Numerous Options for Radiolabeled Peptide Production Because of their established safety, development, and design history, and “the fact that there are many RGD-based tracers with known pharmacokinetics, it can be useful to use them in the imaging of diseases that currently have no accurate method of diagnosis available.”6 However, there are barriers to synthesizing radiolabeled peptides: itcan be a time-consuming, complex, multi-step process. It is also highly variable based on the peptide. Other drawbacks include the intricacies of radiolabeling and the lack of automation for some of these protocols.
Fortuitously, RGDs radiopeptides are not the only ones exhibiting exciting potential for diagnostic imaging and targeted radionuclide therapies.An extensive review article from Paweł Kręcis et al. that appeared in Bioconjugate Chemistry is recommended, as it presents some developments and perspectives in both aforementioned areas regarding the research on somatostatin, bombesin, vasoactive intestinal peptide, gastrin, neurotensin, and exendin peptide analogs, among others.11 It includes the application of radiolabeled peptides and antibodies and an analysis of clinical trials reported in 2008-2018.
Finally, just a few of the current companies doing interesting things in radiopharmaceuticals include Aktis Oncology, Mariana Oncology, Point Biopharma, and Rayze Bio. AMPAC Fine Chemical and AMPAC Analytical, both SK pharmteco companies, have been at the vanguard of small molecule and analytical developments utilizing innovative technologies and techniques directed by teams with decades of experience. If you have a radiolabeled peptide targeted for development, our teams can design, validate, optimize, and analyze your project, ranging from research to commercial quantities. Contact us today for more information.