The role of UHPLC in pharmaceutical development

Pharmaceutical separations can be divided into three categories: high throughput, high productivity, and high resolution. These categories contain specific pharmaceutical applications, each of which has distinct separation goals. Traditionally, these goals have been achieved utilizing conventional HPLC with typical column dimensions and particle sizes. The recent introduction of ultra-HPLC (UHPLC) has provided a new potential for method development and analysis. Pharmaceutical chemists must determine the impact of this emerging technology. UHPLC is achieved by using sub-2 microm particle size column packing at increased linear velocities. In order to utilize this technology, mobile phase viscosity must be minimized or the chromatography system must be redesigned to withstand an increased backpressure. Today, there are many commercially available UHPLC systems capable of exceeding conventional pressure limits of 400 bar. The advantage of UHPLC over conventional HPLC is the capability to increase the speed without sacrificing efficiency. In comparison to traditional HPLC, our research showed that UHPLC can decrease run times up to 7 x. In addition, for high resolution applications, UHPLC achieved significant efficiency advantages over traditional HPLC. This paper will evaluate the potential roles for utilizing UHPLC in the pharmaceutical industry.     

Place of DSC purity analysis in pharmaceutical development

DSC purity analysis is based on thermodynamic phase diagrams for substances (purity ≥98%) which undergo a melting point. Impurities which have eutectic behaviour with the analyte are determined together. DSC purity analysis obtained from a single melting event of a 1–2 mg sample is, therefore, extremely attractive for the global assessment of eutectic impurities. The main advantages in early development lie in the very small amount of material necessary and the very fast analysis time. However, the DSC purity analysis cannot replace chromatographic methods which deliver specific individual levels of impurities. Furthermore, a complete validation of a DSC purity method is difficult and time consuming. Despite these limitations, DSC is the best support for the development of chromatographic methods, for purity profile and stability assessment during pharmaceutical development. Parameters of purity determination and validation aspects are discussed. Examples of use in pharmaceutical development are given.     

Use of ultra-performance liquid chromatography in pharmaceutical development

Ultra-performance liquid chromatography (UPLC) has been investigated as an alternative to HPLC for the analysis of pharmaceutical development compounds. We present data on three compounds showing that significant reductions in separation time can be achieved without compromising the separation quality. Results from precision and comparative studies indicate that UPLC is a suitable technique for routine pharmaceutical analysis.     

Advancing cellulose-based nanotechnology

Nanotechnology has applications across most economic sectors and allows the development of new enabling science with broad commercial potential. Cellulose and lignocellulose have great potential as nanomaterials because they are abundant, renewable, have a nanofibrillar structure, can be made multifunctional, and self-assemble into well-defined architectures. To exploit their potential, R&D investments must be made in the science and engineering that will fully determine the properties and characteristics of cellulose and lignocellulose at the nanoscale, develop the technologies to manipulate self-assembly and multifunctionallity, and develop these new technologies to the point where industry can produce advanced and cost-competitive cellulose and lignocellulose-based products. Because many of the findings on nanostructues and nanoprocesses are not yet fully measurable, replicable, or understood, it will take substantial R&D investments. To most effectively and efficiently move forward, increased cooperation must occur among the cellulose/lignocellulose R&D community, the federal departments and agencies having interests and ongoing programs in nanotechnology, and industry. Cooperation is critical to capturing synergies, enhancing accomplishments, and avoiding unwarranted duplication of facilities and efforts.     

HPLC-SPE-NMR in pharmaceutical development: capabilities and applications

High-performance liquid chromatography-solid phase extraction-NMR spectroscopy (HPLC-SPE-NMR) has recently become commercially available and has been evaluated with regard to its applicability in a pharmaceutical environment. The addition of an automated SPE unit to an HPLC-NMR system for peak trapping results in an improved NMR signal-to-noise ratio (S/N) and also has other practical advantages. The trapping efficiency is shown to depend on compound polarity and is highest for compounds eluting late on reversed-phase HPLC systems. Multiple peak trapping further increases the S/N, again with the best results for less polar compounds. For polar compounds, multiple peak trapping resulted in no S/N gain as the amount of material retained on the SPE cartridge was equivalent to that from a single injection. When compared with conventional HPLC-NMR, a S/N gain of up to five-fold could be achieved for some compounds in a single trapping step. A major advantage of the technique is the independence of the chromatographic step from the NMR step, resulting in greater versatility than conventional HPLC-NMR in the HPLC solvents and NMR solvents that can be used. Practical applications from both drug metabolite and drug impurity identification are presented.     

Perspectives in the development of the theory of spark-source and laser-plasma source mass-spectrometry

The processes of substance evaporation and atom ionization under different conditions of spark discharge or laser radiation are considered. It is shown that the dependence of the relative sensitivity coefficients on the properties of an element can be presented as the product of two exponents with parameters proportional to the atomization energies and first ionization potentials of the element. Differences in matrix composition and conditions influencing a sample in the ion source are considered by means of introducing two fitting parameters-atomization and ionization "temperatures"-into these exponents. Experiments carried out with the help of mass-spectrometers with spark and laser ion sources have corroborated the validity of the suggested quasi-equilibrium model and shown the possibility of its application for the improvement of the accuracy of analysis without use of standards as well as for checking the stability of experimental conditions in the process of analysis with standard samples.     

The application of the measurement uncertainty concept to in-process control in pharmaceutical development

 Any analytical data is used to provide information about a sample. The "possible error" of the measurement can be of extreme importance in order to have complete information. The measurement uncertainty concept is a way to achieve quantitative information about this "possible error" using an estimation procedure. On the basis of the analytical result, the chemist makes a decision on the next step of the development process. If the uncertainty is unknown, the information is not complete; therefore this decision might be impossible. The major problem for the in-process control (IPC) procedure is that not only the repeatability but also the intermediate precision (which expresses the variations within laboratories related to different days, different analysts, different equipment, etc.) has to be good enough to make a decision. Unfortunately, the statistical information achieved from one single analytical run only gives information about the repeatability. This paper shows that the estimation of the measurement uncertainty for IPC is a way to solve the problem and gives the necessary information about the quality of the procedure. An example demonstrates that an estimate of uncertainty based on the standard deviations of an analytical method gives a value similar to one based on the standard deviations obtained from a control chart. Therefore, the estimation is both a very useful and also a very cost-effective tool. Though measurement uncertainty cannot replace validation in general, it is a viable alternative to validation for all methods that will never be used routinely. Received: 24 May 1996 Accepted: 10 August 1996     

Study of the composition of biologically active compounds in chaga meal. Perspectives of application of chaga meal in pharmaceutical industry

Methods of utilization of chaga meal are reviewed. Extraction of chaga meal with ethanol, chloroform, and tert-butyl methyl ether gives compounds possessing a high antioxidant activity. A wide spectrum of other biologically active compounds was found in these extracts. These compounds can be used for production of drugs and biologically active additives.     

Synthetic pharmaceutical peptides characterization by chromatography principles and method development

As per the United States Food and Drug Administration, any polymer/chain composed of 40 or fewer amino acids is called a peptide, where more than 40 amino acids are considered proteins. On many occasions, there is a change in the source of manufacturing of the peptide active pharmaceutical ingredient, where one has to prove the sameness of that product with the existing formulation by considering several aspects like the presence of impurities/degradation products, the extent of aggregations, and so forth. For the same, several chromatographic characterization techniques such as reversed-phase high-performance liquid chromatography-ultraviolet/high-resolution mass spectrometry, supercritical fluid chromatography, size-exclusion chromatography, ion-exchange chromatography, and so forth, are widely used in the pharmaceutical industry. It is well known that the method development of peptide molecules is often challenging as many variables are to be kept in mind which can affect the separation, recovery, and stability of the molecule. The present review focuses on the basics of peptide degradation and method development by using various chromatographic techniques for characterization. It also covers a deep insight of method development parameters and variables to be considered which might directly or indirectly affect the chromatographic separation and recovery and also provides a guide on the selection of chromatographic parameters.     

Material binding peptides for nanotechnology

Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.     

Application of nanotechnology in CAR-T-cell immunotherapy

It is cellular immunotherapy for the tumor that the in vitro modified immunocytes from patients or donors are reinfused into patients to kill tumor cells. Chimeric antigen receptor T cell (CAR-T) therapy, one of the most successful and representative tumor cellular immunotherapies, is now the weapon for cancer after extensive research. Although CAR-T immunotherapy achieves success in treating relapsed/refractory hematological tumors, its drawbacks, including the poor effect in solid tumors, cytokine release syndrome (CRS) or CAR-T-related encephalopathy syndrome (CRES), on-target, off-tumor effect, and high cost, cannot be overlooked. Nanotechnology is advantageous in the construction of CARs, the transfection of T cells, the expansion, delivery, and antitumor effect of CAR-T cells, and the reduction of CAR-T therapy-associated toxicities. Currently, introducing nanotechnology into CAR-T immunotherapy has already been performed in numerous studies with highly promising results. In this review, we summarized the nanotechnologies used in CAR-T immunotherapy and discussed the challenges and directions of CAR-T immunotherapy combined with nanotechnologies in the future.     

Periodic table of elements and nanotechnology

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Soft nanotechnology with soft nanoparticles

The last decade of research in the physical sciences has seen a dramatic increase in the study of nanoscale materials. Today, "nanoscience" has emerged as a multidisciplinary effort, wherein obtaining a fundamental understanding of the optical, electrical, magnetic, and mechanical properties of nanostructures promises to deliver the next generation of functional materials for a wide range of applications. While this range of efforts is extremely broad, much of the work has focused on "hard" materials, such as Buckyballs, carbon nanotubes, metals, semiconductors, and organic or inorganic dielectrics. Meanwhile, the soft materials of current interest typically include conducting or emissive polymers for "plastic electronics" applications. Despite the continued interest in these established areas of nanoscience, new classes of soft nanomaterials are being developed from more traditional polymeric constructs. Specifically, nanostructured hydrogels are emerging as a promising group of materials for multiple biotechnology applications as the need for advanced materials in the post-genomic era grows. This review will present some of the recent advances in the marriage between water-swellable networks and nanoscience.     

电感耦合等离子体质谱法测定高纯金中铝、砷、铋、铬、铁、铅、锑、硒、碲、铱痕量元素

建立了微波消解-内标法-标准加入-ICP-MS法测定高纯黄金中铝、砷、铋、铬、铁、铅、锑、硒、碲、铱等痕量元素的分析方法。从试样溶解方式、内标元素及同位素的选择、仪器检测模式的优化及降低基体抑制效应等方面进行优化。实验加标回收率为99.5%～110%,相对标准偏差(RSD)为0.050%～6.5%。实验的准确度和精密度良好,操作便捷。     

Dendritic macromolecules at the interface of nanoscience and nanotechnology

As a result of their unique architecture and structural as well as functional versatility, dendrimers have generated considerable interest in numerous areas of the physical sciences, engineering, as well as the biological sciences. Both their size - in the 1-10 nm range - and their globular shape resemble those of many proteins suggesting a host of biomimetic and nanotechnological applications. This brief highlight describes some of our recent work with nascent applications of dendrimers as unimolecular nanoreactors, as nanoscale antennae for energy harvesting and transduction, and as nanosized carriers for diagnostic or therapeutic applications. While implementation of some of these applications may still be distant, the impatient critic might remember that new markets are not created overnight as demonstrated by the slow commercial acceptance of many promising molecules and technologies with development frequently extending decades after their initial discovery.     

Nanoscience,nanotechnology and spectrometry

Nanoscience has outgrown its infancy, and nanotechnology has found important applications in our daily life — with many more to come. Although the central concepts of the nano world, namely the changes of particular physical properties on the length scale of individual atoms and molecules, have been known and developed for quite some time already, experimental advances since the 1980s and recognition of the potential of nanomaterials led to a genuine breakthrough of the inherently multidisciplinary nanoscience field. Analytical nanoscience and nanotechnology and especially the use of micro and nano electro mechanical systems, of the quantum dots and of mass spectrometry, currently provide one of the most promising avenues for developments in analytical science, derived from their two main fields of action, namely (a) the analysis of nano-structured materials and (b) their use as new tools for analysis. An overview is given of recent developments and trends in the field, highlighting the importance and point out future directions, while also touching drawbacks, such as emerging concerns about health and environmental issues.