Proteome of plasma extracellular vesicles as a source of colorectal cancer biomarkers.

The search for minimally invasive methods for diagnostics of colorectal cancer (CRC) is the most important task for early diagnostics of the disease and subsequent successful treatment. Human plasma represents the main type of biological material used in the clinical practice; however, the complex dynamic range of substances circulating in it complicates determination of CRC protein markers by the mass spectrometric (MS) method. Studying the proteome of extracellular vesicles (EVs) isolated from human plasma represents an attractive approach for the discovery of tissue-secreted CRC markers. We performed shotgun mass spectrometry analysis of EV samples obtained from plasma of CRC patients and healthy volunteers. This MS analysis resulted in identification of 370 proteins (which were registered by at least two peptides). Stable isotope-free relative quantitation identified 55 proteins with altered abundance in EV samples obtained from plasma samples of CRC patients as compared to healthy controls. Among the EV proteins isolated from blood plasma we found components involved in cell adhesion and the VEGFA-VEGFR2 signaling pathway (TLN1, HSPA8, VCL, MYH9, and others), as well as proteins expressed predominantly by gastrointestinal tissues (polymeric immunoglobulin receptor, PIGR). The data obtained using the shotgun proteomic profiling may be added to the panel for targeted MS analysis of EV-associated protein markers, previously developed using CRC cell models.

Variation in Shrimp Allergens: Place of Origin Effects on Food Safety Assessment.

Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected by an origin-dependent protein composition. This study determined if the geographic location of capture, or aquaculture, influenced the allergenic protein profiles of Black Tiger Shrimp (Penaeus monodon), one of the most farmed and consumed shrimp species worldwide. Protein composition was analysed in shrimp from nine different locations in the Asia-Pacific by SDS-PAGE, immunoblotting, and mass spectrometry. Ten of the twelve known shrimp allergens were detected, but with considerable differences between locations. Sarcoplasmic calcium-binding protein, myosin light chain, and tropomyosin were the most abundant allergens in all locations. Hemocyanin-specific antibodies could identify up to six different isoforms, depending on the location of origin. Similarly, tropomyosin abundance varied by up to 13 times between locations. These findings suggest that allergen abundance may be related to shrimp origin and, thus, shrimp origin might directly impact the readout of commercial crustacean allergen detection kits, most of which target tropomyosin, and this should be considered in food safety assessments.

A magnetic calcium phosphate for selective capture of multi-phosphopeptides.

The specific enrichment of multi-phosphopeptides in the presence of non-phosphopeptides and mono-phosphopeptides was still a challenge for phosphoproteomics research. Most of these enrichment materials relied on Zn, Ti, Sn, and other rare precious metals as the bonding center to enrich multi-phosphopeptides while ignoring the use of common metal elements. The addition of rare metals increased the cost of the experiment, which was not conducive to their large-scale application in biomedical proteomics laboratories. In addition, multiple high-speed centrifugation steps also resulted in the loss of low-abundance multi-phosphopeptides in the treatment procedure of biological samples. This study proposed the use of calcium, a common element, as the central bonding agent for synthesizing magnetic calcium phosphate materials (designated as CaP-Fe3O4). These materials aim to capture multi-phosphopeptides and identifying phosphorylation sites. The current results demonstrate that CaP-Fe3O4 exhibited excellent selection specificity, high sensitivity, and stability in the enrichment of multi-phosphopeptides and the identification of phosphorylation sites. Additionally, the introduction of magnetic separation not only reduced the time required for multi-phosphopeptides enrichment but also prevented the loss of these peptides during high-speed centrifugation. These findings contribute to the widespread application and advancement of phosphoproteomics research.

Duvelisib: A comprehensive profile.

Duvelisib (DUV) is chemically named as (S)-3-(1-((9H-Purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one. It is a novel drug with a small molecular weight and characterized by dual phosphoinositide-3-kinase (PI3K)- and PI3K-inhibitory activity. The Food and Drug Administration (FDA) recently approved DUV for the management of small lymphocytic lymphoma (SLL) and relapsed or refractory chronic lymphocytic leukemia (CLL) in adult patients. DUV is marketed under the brand name of Copiktra® (Verastem, Inc., Needham, MA, USA). This chapter provides a critical extensive review of the literature, the description of DUV in terms of its names, formulae, elemental composition, appearance, and use in the treatment of CLL, SLL, and follicular lymphoma. The chapter also describes the methods for preparation of DUV, its physical-chemical properties, analytical methods for its determination, pharmacological properties, and dosing information.

Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation.

Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T-cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single-cell RNA-seq, along with multi-omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+ CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T-cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL-4, IL-6, and IL-13), GM-SCF, and IL-1ß. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T-cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12-TNFRSF12A, TNF-TNFRSF1A, and granzyme-gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.

Radiological risk assessment from the Gamma spectrometry of soil samples in the vicinity of a research centre in Nilore, Pakistan.

Measurements of radionuclides' activities in air, water, and soil give clues about the anthropogenic activities in the region, and imperative to assess the overall radiological risk for individuals. Such an investigation was carried out to characterize the soil activities in the region hosting a research center, and to calculate the associated elements of radiological risk in terms of radiation doses and hazard indices. The soil samples were collected within the radius of 10 km in local area, Nilore, and analysed for activity using a high-purity germanium (HPGe) gamma spectrometric system. In all samples, only the basic nuclides, contributing to terrestrial activity, i.e., 40 K, 232Th, 226Ra, and 137Cs, were observed within the detectable limits of activity. The distribution of the data set and the correlation between the measured activities were studied with the use of the principal component analysis (PCA). The measured average specific activities of 226Ra, 232Th, 40 K, and 137Cs were 40.65 ± 9.84 Bq/kg, 59.31 ± 16.53 Bq/kg, 528.24 ± 131.18 Bq/kg, and 5.16 ± 4.56 Bq/kg respectively. The corresponding dose rate in air was found to be 76.63 ± 18.39 nGy/h, which is slightly higher than the world median value of 51 nGy/h calculated from concentration of terrestrial radionuclides in soil but falls within the world average value range of outdoor external exposure of 18-93 nGy/h obtained through direct measurement, and therefore not harmful for the living species. The standard hazard indices for all soil samples such as radium equivalent activity ([Formula: see text]), external hazard index (Hex), and internal hazard index (Hin) were also found within safe limits for the soil to be used as construction of building material. This investigation led to conclusion that the soil activities are consistent with the usual background level of terrestrial activities, and their associated dose rates are well within the safe limits for public.

Brimonidine.

Brimonidine is a highly selective 2-adrenoceptor agonist that lowers intraocular pressure (IOP) by decreasing aqueous humor production and increasing aqueous humor outflow via the uveoscleral route. Brimonidine is used to treat glaucoma and other eye conditions. Brimonidine is a topical medication that is used mainly to treat open-angle glaucoma and ocular hypertension in the eyelids. The purpose of this chapter is to provide a comprehensive discussion of Brimonidine's nomenclature, physiochemical properties, preparation methods, identification procedures, and numerous qualitative and quantitative analytical techniques, as well as its ADME profiles and pharmacological effects. In addition, the chapter contains numerous approaches for separating brimonidine from other medications in combination formulations utilizing chromatographic techniques and other spectroscopic approaches.

Remdesivir.

Remdesivir, marketed under the brand name Veklury, is an antiviral drug with a broad spectrum of activity. There were various countries where the use of Remdesivir for the treatment of COVID-19 was authorized during the pandemic. Remdesivir was first designed to treat hepatitis C, but it was later tested for Ebola virus sickness and Marburg virus infections. Remdesivir is a prodrug designed to facilitate the intracellular transport of GS-441524 monophosphate and its subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase. The objective of this chapter is to provide a comprehensive review of Remdesivir (GS-5734), including its nomenclature, physiochemical properties, preparation methods, identification procedures, numerous qualitative and quantitative analytical techniques, ADME profiles, and pharmacological effects. In addition, the chapter provides a variety of chromatographic and spectroscopic techniques for separating brimonidine from other drugs in combination formulations.

Molecular Profiling of Athletes Performing High-Intensity Exercises in Extreme Environments.

The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes (n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.

Advances in mass-encoded probes for multiplex mass spectrometric detection / 中国药科大学学报

@#Mass-encoded probe is a probing tool that specifically identifies target molecules and thus outputs their characteristic ion signals with mass tags.It plays an important role in multiplex assay of disease markers, drug target screening and other biomedical applications.Based on various mass spectrometric methods, researchers have developed an array of mass tag-encoded probes with different structures and functions, providing powerful technical tools for multiplex detection of biomolecules in physiological environments and for mass spectrometry imaging of tissue samples.This review introduces the latest research progress of mass tag-encoded probes in multiplex mass spectrometric detection from three aspects, i.e. structural composition of the probes, mass spectrometric methods and their application in biochemical analysis, with a prospect of the future development of mass tag-encoded probes.

Characterisation of teaghrelin-like principles from Assam tea cultivated in Thailand.

Teaghrelins were identified as unique acylated flavonoid tetraglycosides and firstly reported in Chin-shin oolong tea. In the present study, two new teaghrelin-like compounds (1 and 2) were purified and characterised from Assam tea varieties collected in Thailand. Their chemical structures were constructed by the spectroscopic and spectrometric analysis. These two teaghrelin-like compounds were also not supposed to exhibit significant ghrelin receptor affinity according to the structural comparison with those teaghrelin-like compounds previously reported. In addition, compounds 1 and 2 did not display notable anti-inflammatory activity in human neutrophils assay.[Formula: see text].

Potential DPP IV Inhibitory Peptides from Dry-Cured Pork Loins after Hydrolysis: An In Vitro and In Silico Study.

Peptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes, and inhibitors of this enzyme are an important class of drugs for the treatment of type 2 diabetes. In the present study, peptides (<7 kDa) isolated from dry-cured pork loins after pepsin and pancreatin hydrolysis were identified by mass spectrometry and tested as potential inhibitors of DPP-IV by the in silico method. Two peptides, namely WTIAVPGPPHS from myomesin (water-soluble fraction, A = 0.9091) and FKRPPL from troponin (salt-soluble fraction, A = 0.8333), were selected as the most promising inhibitors of DPP-IV. Both peptides were subjected to ADMET analysis. Fragments of these peptides showed promising drug-likeness properties as well as favorable absorption, distribution, metabolism, excretion, and toxicity functions, suggesting that they are novel leads in the development of DPP-IV inhibitors from food.

Characterization of Conjugates between α-Lactalbumin and Benzyl Isothiocyanate-Effects on Molecular Structure and Proteolytic Stability.

In complex foods, bioactive secondary plant metabolites (SPM) can bind to food proteins. Especially when being covalently bound, such modifications can alter the structure and, thus, the functional and biological properties of the proteins. Additionally, the bioactivity of the SPM can be affected as well. Consequently, knowledge of the influence of chemical modifications on these properties is particularly important for food processing, food safety, and nutritional physiology. As a model, the molecular structure of conjugates between the bioactive metabolite benzyl isothiocyanate (BITC, a hydrolysis product of the glucosinolate glucotropaeolin) and the whey protein α-lactalbumin (α-LA) was investigated using circular dichroism spectroscopy, anilino-1-naphthalenesulfonic acid fluorescence, and dynamic light scattering. Free amino groups were determined before and after the BITC conjugation. Finally, mass spectrometric analysis of the BITC-α-LA protein hydrolysates was performed. As a result of the chemical modifications, a change in the secondary structure of α-LA and an increase in surface hydrophobicity and hydrodynamic radii were documented. BITC modification at the ε-amino group of certain lysine side chains inhibited tryptic hydrolysis. Furthermore, two BITC-modified amino acids were identified, located at two lysine side chains (K32 and K113) in the amino acid sequence of α-LA.

[Recent advances in glycopeptide enrichment and mass spectrometry data interpretation approaches for glycoproteomics analyses].

Protein glycosylation is one of the most important post-translational modifications (PTMs). The glycosylation is crucial in a variety of physiological and pathological processes that include protein stability, intracellular and intercellular signal transduction, hormone activation or inactivation, and immune regulation. Protein glycosylation is generated by complex biosynthetic pathways comprising hundreds of glycosyltransferases, glycosidases, transcriptional factors, transporters, and protein backbones. Abnormal protein glycosylation is closely associated with the occurrence and development of diseases. Many disease biomarkers in clinical screening are glycoproteins (alfa fetoprotein for liver cancer, carbohydrate antigen 125 for ovarian cancer, carcinoembryonic antigen for colon cancer, prostate-specific antigen for prostate cancer, etc.), and glycan antigens (carbohydrate antigen 19-9 for gastrointestinal cancer and pancreatic cancer, etc.). Glycoproteomics research and technological developments are important to elucidate the mechanism of protein glycosylation in vivo. Mass spectrometry (MS)-based proteomics provides an excellent approach for the comprehensive analysis of proteins and their modifications. In bottom-up proteomics, glycoproteomic analysis is more difficult than other PTMs because intact glycopeptides have diverse peptide backbones and glycan chains, relatively low abundance and ionization efficiency, and pronounced heterogeneity. In recent years, glycoproteomic methodologies such as intact glycopeptide enrichment methods, MS fragmentation and acquisition approaches, MS data interpretation tools and software, and quantification strategies have been appreciably improved. These methodologies have driven in-depth glycoproteomics research. This review focuses on the recent advances in MS-based glycoproteomics. New enrichment methods and spectral interpretation approaches of intact N- and O-glycopeptides are discussed. Their applications in answering various questions in complex biological systems are also considered. The new enrichment methods for intact glycopeptides are mostly based on existing principles. Some properties of the materials, such as hydrophilicity and electrophilicity, have been optimized to improve the enrichment performance. For example, dual-functional Ti(IV)-IMAC materials have been used for the separation of glycopeptides and phosphopeptides. Considering the clinical applications, some glycoproteomics methods integrate enrichment processing into automated workflows to reduce errors caused by manual operations and to increase the experimental reproducibility and efficiency. For example, an automated glycopeptide enrichment method consisting of a liquid chromatograph equipped with a hydrophilic interaction chromatography column has been shown capable of highly reproducible analyses of site-specific glycopeptides in complex biological samples. These methods are more suitable for the discovery of newly glycosylation-related biomarkers as well as for the physiopathological studies of human diseases. With the optimization of glycopeptide enrichment methods and the innovation of MS technologies in the past decade, MS analysis of intact glycopeptides has begun to yield a wealth of glycopeptide fragment ions and plentiful high-quality MS data. This review introduces several effective fragmentation methods for intact glycopeptides. These include collision-induced dissociation, high-energy collision dissociation, electron capture dissociation, electron-transfer dissociation, and electron-transfer/higher-energy collision dissociation. Automated analysis of MS data of intact N- and O-glycopeptides requires interpretation approaches and corresponding software tools with high sensitivity and reliability. Finally, we highlight the utility of several spectral interpretation approaches and their corresponding popular search software, including ArMone, Byonic, GPQuest, pGlyco, O-search, MSFragger-Glyco, and O-Pair Search. In addition, MS data acquisition modes, such as data-dependent acquisition, data-independent acquisition, multiple reaction monitoring technology, and parallel reaction monitoring technology, have great application prospects in glycoproteomics research. With the improvements in enrichment methods, MS technologies, and spectral interpretation approaches for intact N- and O-glycopeptides, comprehensive and systematic glycoproteomics analysis has tremendously expanded the knowledge of protein glycosylation. These glycoproteomic technologies have a wide range of applications that include exploring the molecular mechanisms of protein glycosylation and discovering the new biomarkers of human diseases.

A new Ti-based IMAC nanohybrid with high hydrophilicity and enhanced absorption capacity for the selective enrichment of phosphopeptides.

Ti-based immobilized metal affinity chromatography (IMAC) nanomaterial has shown high potential in phosphoproteome mass-spectrometric (MS) analysis. However, the limited surface area and poor solubility will greatly restrict its use in phosphoproteome research. To overcome these two key drawbacks, a novel Ti-based IMAC nanomaterial was prepared by Ti-bonded ß-cyclodextrin (ß-CD) anchored on the surface of carbon nanotubes (CNTs) (denoted as COOH-CNTs-CD-Ti) and successfully applied as a biofunctional adsorbent for selectively enriching trace phosphopeptides. In the selective enrichment process, CNTs provided greater surface area for the absorption of phosphopeptides, while ß-CD also offered a greater opportunity for the interaction between phosphopeptides and Ti4+. COOH-CNTs-CD-Ti with the aforementioned properities exhibited higher selectivity for phosphopeptides from the standard protein digests, the tryptic digests of nonfat milk and human serum, showing a great selective enrichment capability towards complex biological samples.

Electrostatic spray drying for monoclonal antibody formulation.

This study explored the feasibility of electrostatic spray drying for producing a monoclonal antibody (mAb) powder formulation at lower drying temperatures than conventional spray drying and its effect on protein stability. A mAb formulation was dried by either conventional spray drying or electrostatic spray drying with charge (ESD). The protein powders were then characterized using solid-state Fourier transform infrared spectroscopy (ssFTIR), differential scanning calorimetry (DSC), size exclusion chromatography (SEC), and solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS). Particle characterizations such as BET surface area, particle size distribution, and particle morphology were also performed. Conventional spray drying of the mAb formulation at the inlet temperature of 70 °C failed to generate dry powders due to poor drying efficiency; electrostatic spray drying at the same temperature and 5 kV charge enabled the formation of powder formulation with satisfactory moisture contents. Deconvoluted peak areas of deuterated samples from the ssHDX-MS study showed a good correlation with the loss of the monomeric peak area measured by size exclusion chromatography in the 90-day accelerated stability study conducted at 40 °C. Low-temperature (70 °C inlet temperature) drying with an electrostatic charge (5 kV) led to better protein physical stability as compared with the samples spray-dried at the high temperature (130 °C inlet temperature) without charge. This study shows that electrostatic spray drying can produce solid monoclonal antibody formulation at lower inlet temperature than traditional spray drying with better physical stability.

Analytical method for the simultaneous determination of a broad range of opioids in influent wastewater: Optimization, validation and applicability to monitor consumption patterns.

Wastewater-based epidemiology (WBE) employs the analysis of human metabolic biomarkers in influent wastewater (IWW) to estimate community-wide exposure to xenobiotics (e.g. prescription opioids). The low ng/L range of concentrations of these biomarkers and the complex matrix composition pose bioanalytical challenges related to sample preparation and detection/quantification. Therefore, a sensitive analytical method for the detection and analysis of 19 opioid biomarkers was optimized and validated according to the European Medicines Agency guidelines. Oasis HLB cartridges were used for sample concentration and an Atlantis T3 column with gradient elution resulted in sufficient separation of the analytes. Absolute recoveries (RE) were highly reproducible and ranged between 50 and 93% with the exception of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The lower limit of quantification (LLOQ) ranged between 1 and 100 ng/L and was based on the analyte concentrations found in IWW. Process efficiency was acceptable for all biomarkers for which an isotope-labelled deuterated analogue was available. All biomarkers showed high benchtop stability with the exception of buprenorphine, EDDP, fentanyl and normorphine. Apart from buprenorphine and hydrocodone, all analytes under investigation were detected at least once above LLOQ levels in five locations in Belgium. The highest population-normalized mass loads were found for tramadol, O-desmethyltramadol and codeine. The proposed methodology was able to evaluate spatial differences in opioid use.

An In Vivo Spectrophotometric Analysis of Gingival Acrylic Shade Guide.

Selecting shades of acrylic gingival restorative material is challenging. This study examined the shade appropriateness of five acrylic gingival restorative materials. The color was analyzed using an intraoral spectrophotometer (Crystaleye®, Olympus). The gingival color of maxillary incisors for eighty-nine patients was measured. CIELAB color coordinates (L*, a* and b*) were obtained, and the color difference ∆E (Coverage Error: CE) between shade tabs and natural gingival color of patient samples for each shade guide system were compared. Repeated ANOVA and post hoc analyses with Tukey's HSD were performed. There was a significant difference among the mean minimum CEs of the tab sets (p < 0.01). GC Acrylic (CE = 5.89 ∆E ± 2.97) and Lucitone 199® (CE = 6.55 ± 3.33) groups exhibited CEs significantly lower than all other groups (all p < 0.001). The IvoCap® system exhibited the highest CE (10.78 ± 3.80), significantly greater than all other groups (p < 0.001). No significant differences were observed based on sex (p = 0.055) or ethnicity (p = 0.327). The GC Acrylic and Lucitone 199® shade guides showed the lowest CEs. All guides had coverage errors above 5.89 ∆E, which is larger than ∆E thresholds of acceptability. Of the materials evaluated in this study, GC Acrylic and Lucitione 199® are best able to reproduce the clinical appearance of the gingival tissue. Many patients have tissue that cannot be reproduced accurately with currently available materials.

Darunavir: A comprehensive profile.

Darunavir: (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-4-{[(4-aminophenyl)sulfonyl] (isobutyl)amino}-3-hydroxy-1-phenyl-2-butanyl]carbamate is a synthetic non-peptide protease inhibitor. On June 2006, it was first approved by the Food and Drug administration (FDA) for treatment of resistant type-1 of the human immunodeficiency virus (HIV). In July 2016, the FDA expanded the approval for use of darunavir in pregnant women with HIV infection. Darunavir prevents the replication of HIV virus by inhibiting the catalytic activity of the HIV-1 protease enzyme, and selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Darunavir is unique among currently available protease inhibitors because it maintains antiretroviral activity against a variety of multidrug-resistant HIV strains. This article discusses, by a critical extensive review of the literature, the description of darunavir in terms of its names, formulae, elemental composition, appearance, and use in the treatment of HIV-infected patients. The article also discusses the methods for preparation of darunavir, its physical-chemical properties, analytical methods for its determination, pharmacological properties, and dosing information.

Irbesartan (a comprehensive profile).

Irbesartan, (2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one), is a member of non-peptide angiotensin II receptor antagonists used worldwide in the treatment of hypertension and diabetic nephropathy in hypertensive patients with type 2 diabetes, elevated serum creatinine, and proteinuria. Irbesartan can be used alone or in combination with other antihypertensive agents (e.g., hydrochlorothiazide). These combination products are indicated for hypertension in patients with uncontrolled hypertension with monotherapy or first line in patients not expected to be well controlled with monotherapy. Irbesartan is also indicated for the treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension, an elevated serum creatinine, and proteinuria. Irbesartan exerts its action mainly via a selective blockade action on AT1 receptors and the consequent reduced pressor effect of angiotensin II. This article discusses, by a critical comprehensive review of the literature on irbesartan in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of irbesartan, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information.