Pharmaceutical Drug Development Research Articles

Extraction and Identification of Antioxidant Ingredients from Cyclocarya paliurus (Batal.) Iljinsk Using UHPLC-Q-Orbitrap-MS/MS-Based Molecular Networking

Cyclocarya paliurus (Batal.) Iljinskaja (LCP) leaves have been widely employed in food and traditional medicine for treating hyperlipidaemia and its complications, possibly owing to their antioxidant properties. The aim of the present study is to identify the chemical ingredients of antioxidant extracts from LCP by using UHPLC-Q-Orbitrap-MS/MS-based molecular networking, a very recent and useful tool for annotation of chemical constituents in mixtures. The extraction conditions of antioxidant extracts from LCP were optimised by single-factor analysis and response surface methodology (RSM). The optimised conditions were a methanol concentration of 32%, a liquid-to-solid ratio of 0.4 ml/mg, an extraction temperature of 25°C, and an extraction time of 32 min. Under these conditions, the antioxidant yield was 516.20 ± 28.52 μmol TE/ml. The main active ingredients in the antioxidants were identified by UHPLC-Q-Exactive Orbitrap-MS-based molecular networking. In total, 42 compounds were identified, including 20 flavonoids, 16 quinic acid derivatives, 4 caffeoyl derivatives, and 2 coumaroyl derivatives. The findings of the present work suggest that LCP could be a suitable source of natural antioxidant compounds, which might be applicable in the development of potential pharmaceutical drugs targeting diseases related to oxidative stress.

Statistical modeling approaches for the comparison of dissolution profiles.

Dissolution studies are a fundamental component of pharmaceutical drug development, yet many studies rely upon the and model-independent approach that is not capable of accounting for uncertainty in parameter estimation when comparing dissolution profiles. In this paper, we deal with the issue of uncertainty quantification by proposing several model-dependent approaches for assessing the similarity of two dissolution profiles. We take a statistical modeling approach and allow the dissolution data to be modeled using either a Dirichlet distribution, gamma process model, or Wiener process model. These parametric forms are shown to be reasonable assumptions that are capable of modeling dissolution data well. Furthermore, based on a given statistical model, we are able to use the difference factor and similarity factor to test the equivalency of two dissolution profiles via bootstrap confidence intervals. Illustrations highlighting the success of our methods are provided for both Monte Carlo simulation studies, and real dissolution data sets.

Precision Nanotoxicology in Drug Development: Current Trends and Challenges in Safety and Toxicity Implications of Customized Multifunctional Nanocarriers for Drug-Delivery Applications.

The dire need for the assessment of human and environmental endangerments of nanoparticulate material has motivated the formulation of novel scientific tools and techniques to detect, quantify, and characterize these nanomaterials. Several of these paradigms possess enormous possibilities for applications in many of the realms of nanotoxicology. Furthermore, in a large number of cases, the limited capabilities to assess the environmental and human toxicological outcomes of customized and tailored multifunctional nanoparticles used for drug delivery have hindered their full exploitation in preclinical and clinical settings. With the ever-compounded availability of nanoparticulate materials in commercialized settings, an ever-arising popular debate has been egressing on whether the social, human, and environmental costs associated with the risks of nanomaterials outweigh their profits. Here we briefly review the various health, pharmaceutical, and regulatory aspects of nanotoxicology of engineered multifunctional nanoparticles in vitro and in vivo. Several aspects and issues encountered during the safety and toxicity assessments of these drug-delivery nanocarriers have also been summarized. Furthermore, recent trends implicated in the nanotoxicological evaluations of nanoparticulate matter in vitro and in vivo have also been discussed. Due to the absence of robust and rigid regulatory guidelines, researchers currently frequently encounter a larger number of challenges in the toxicology assessment of nanocarriers, which have also been briefly discussed here. Nanotoxicology has an appreciable and significant part in the clinical translational development as well as commercialization potential of nanocarriers; hence these aspects have also been touched upon. Finally, a brief overview has been provided regarding some of the nanocarrier-based medicines that are currently undergoing clinical trials, and some of those which have recently been commercialized and are available for patients. It is expected that this review will instigate an appreciable interest in the research community working in the arena of pharmaceutical drug development and nanoformulation-based drug delivery.

Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications.

Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.

Sequential Bayes Factors for Sample Size Reduction in Preclinical Experiments with Binary Outcomes

Preclinical studies are an integral part of pharmaceutical drug development, yet traditional methods for designing and analyzing these types of studies can be inefficient and wasteful. Even worse, when the units of study are animals, ethical concerns can arise. The 3Rs initiative was established for the ethical treatment of animals through the replacement, reduction, and refinement of animal experiments. In this article, we focus on the reduction aspect of the 3Rs initiative through the use of sequential Bayes factors. The use of sequential Bayes factors has the potential to help design more efficient experiments, that can be analyzed sequentially, in order to reduce the average number of animals needed in preclinical studies. An added bonus, sequential Bayes factors provide a means of quantifying evidence both for and against the null hypothesis, a characteristic not common to traditional preclinical trial analysis methods. Illustrations highlighting the success of sequential Bayes factors are provided for two real seven-day preclinical experiments in rats, as well as extensive simulation studies.

S2126 Sevelamer-Induced Colitis

Introduction: Drug-induced Gastrointestinal (GI) injury has been well established throughout the literature and continues to prevail with the ever-growing expansion of pharmaceutical drug development. Mucosal injuries due to medications ranging from common over-the-counter drugs to novel chemotherapeutics, have been one of the more common findings seen both endoscopically and histologically in drug-induced GI injury. Though frequently seen with NSAIDs, iron pills, and bisphosphonates, lately, resin-based binders like Sevelamer have shown an increased incidence of GI mucosal injuries. Sevelamer is an oral phosphate binder widely used to treat hyperphosphatemia in patients with chronic kidney disease. Here we present a case of Sevelamer induced colitis in a patient on Sevelamer Carbonate therapy for hyperphosphatemia secondary to acute kidney injury. Case Description/Methods: 34 year old male with history of hypertension, obesity class III status post sleeve gastrectomy, OSA, congestive heart failure, and a recent diagnosis of COVID-19 was admitted to the MICU for acute hypoxemic respiratory failure requiring intubation. His hospital course was complicated by worsening renal function and oliguria with creatinine 8.9 and phosphorus 6.4. He was started on hemodialysis (HD), followed by Sevelamer Carbonate 0.8 g TID then increased to 1.6 g TID. Weeks after initiating HD, he developed bright red blood per rectum requiring intermittent transfusions. CT abdomen pelvis and mesenteric angiogram were unremarkable. Upper GI endoscopy showed a Forest Class III duodenal ulcer. Colonoscopy showed localized severe friable ulcerated mucosa with loss of vascular pattern in the cecum and ascending colon. Biopsy at these sites revealed mucosal ulcerations with granulation tissue with Sevelamer crystal deposits. Hematochezia improved on discontinuing Sevelamer (Figure). Discussion: Sevelamer is a calcium-free oral phosphate binder that has replaced calcium-based binders to treat hyperphosphatemia. Common side effects include nausea, vomiting, and diarrhea. GI mucosal injury from resin-based binders has been reported, although colitis induced by Sevelamer crystal deposition is rare. Previous literature shows a wide range of presentations, including ulcerations, GI bleeding, and colonic strictures. As with prior reports, we show similar endoscopic and histological findings from our patient consistent with this rare entity.Figure 1.: A, Colonoscopic finding showing erythematous ulcerated mucosa in the proximal ascending colon. B, Biopsy from proximal ascending colon site showing granulation tissue with ulceration. The black arrow indicates the Sevelamer Crystal deposition, showing the characteristic “Fish Scale” pattern.

Reproductive, antioxidant, anti-inflammatory, antimicrobial, protective and antidiabetic activities of Helichrysum Mill. species

South African Helichrysum species are known for diverse medicinal use and treatment of different illnesses. Ethnopharmacological studies have revealed the potential use of Helichrysum plants in drug discovery. Although some of these species have been documented, there is still paucity of information on most species. This review seeks to provide a compilation of documented traditional uses, reproductive potential, antioxidant, anti-inflammatory, antimicrobial, protective and antidiabetic activities and other therapeutic properties of some Helichrysum species of South Africa. Information on Helichrysum cymosum, H. foetidum, H. odoratissimum, H. patulum and H. petiolare were collected from such scientific databases as Google scholar, Scifinder, PubMed, Elsevier, Scopus, Science direct in the form of journal articles, scientific reports, theses and books from the Library of the Cape Peninsula University of Technology. Our findings show that these species have historic values in traditional medicine through their diverse use for the management and treatment of such illnesses as cold, diabetes, headaches, digestive problems, sores and wounds, HIV, cancer etc. Additionally, the reported bioactive constituents isolated from these species have been shown to indicate several activities such as antimicrobial, antioxidant, antidiabetic, neuroprotection, reproductive potentials and others. Thus, the current review highlights the phytochemical and bioactive constituents as well as some of the pharmacological properties of the five selected Helichrysum species with a view to providing validation for their use in the pharmaceutical drug development process.

32877 Dermatology clinical trials: Analysis of investments by the top 10 pharmaceutical companies

Introduction: Pharmaceutical drug development is essential for dermatological advancements. There is a lack of diversity among drugs developed and a limited range of diseases targeted which is partly attributable to economic considerations. Herein, we analyzed patterns and characteristics of dermatologic clinical trials undertaken by the top 10 pharmaceutical companies globally.

Inter-organizational Information Systems and Trust: A Study of Pharmaceutical Outsourcing

The abilities of increasingly sophisticated inter-organizational information management technologies to monitor vendors’ work processes have led many organizations to overcome the fears traditionally associated with non-hierarchical exchange arrangements for sensitive and complex functions like research and development. In this paper, we explore how the properties of information technology influence the conditions for trust building in the outsourcing of R&D. The paper draws on affordance theory to analyze how the IS creates conditions for rational-economic trust and social trust. We perform an interview-based study of the role of laboratory management systems in pharmaceutical drug development outsourced by Western big pharma to contract research organizations in India. Empirical findings show how the IS reduces the need for rational-economic trust by affording real-time and retrospective monitoring as well as by largely eliminating the threat of appropriation by affording modularization of work. The findings also show attempts to circumvent the monitoring elements of the IS, illustrating the limits of the information system. This creates space for social trust and the findings show how the IS affords social trust building by structuring interaction and promoting transparency.

Some uses of predictive probability of success in clinical drug development

Predictive probability of success is a (subjective) Bayesian evaluation of the prob- ability of a future successful event in a given state of information. In the context of pharmaceutical clinical drug development, successful events relate to the accrual of positive evidence on the therapy which is being developed, like demonstration of su- perior efficacy or ascertainment of safety. Positive evidence will usually be obtained via standard frequentist tools, according to the regulations imposed in the world of pharmaceutical development.Within a single trial, predictive probability of success can be identified with expected power, i.e. the evaluation of the success probability of the trial. Success means, for example, obtaining a significant result of a standard superiority test.Across trials, predictive probability of success can be the probability of a successful completion of an entire part of clinical development, for example a successful phase III development in the presence of phase II data.Calculations of predictive probability of success in the presence of normal data with known variance will be illustrated, both for within-trial and across-trial predictions.

Contribution of Humanized Liver Chimeric Mice to the Study of Human Hepatic Drug Transporters: State of the Art and Perspectives.

Chimeric mice with humanized livers constitute an attractive emergent experimental model for investigating human metabolism and disposition of drugs. The present review was designed to summarize key findings about the use of this model for studying human hepatic drug transporters, which are now recognized as important players in pharmacokinetics and consequently have to be considered from a regulatory perspectiveduring pharmaceutical drug development. The reviewed data indicate that chimeric mice with humanized livers have been successfully used for analysing the implications of human hepatic drug transporters for drug hepatobiliary elimination, drug-drug interactions and drug-induced cholestasis. Such transporter studies have been performed in vivo with chimeric mice and/or in vitro with human hepatocytes isolated from humanized liver and used either in suspension or in culture. The residual presence of mouse hepatocytes and the potential morphological/histological alterations of the humanized liver, as well as its immunodeficient mouse environment, have, however, to be considered when using chimeric mice with humanized livers for transporter studies. Finally, if the proof of concept of applying chimeric mice with humanized livers to hepatic drug transport is established, more experimental data on this topic, including from standardization approaches, are likely required to completely and accurately demonstrate the robustness, convenience and added value of this chimeric mouse model for drug transporter studies.

Development of a method for determining the morpholinium thiazotate using more economic and green GC/MS assay with an fid detector

One of the main steps in the pharmaceutical development of drugs is the choice of quality control methods. The correctness of the method must be confirmed by validation. In addition, manufacturers take into account various economic and environmental factors. It is especially important to determine the above aspects for domestic and promising drugs, such as the morpholinium thiazotate. The aim. During the development of methods for the routine analysis of medicinal products, attention should be paid to efficiency of analysis, budget, as well as their impact to the environment. Because of this reason, not only new methods for routine analysis should be developed. It is important this methods must be environmentally-friendly and cost-efficient. Materials and methods. The determination of the morpholinium thiazotate was carried out by HPLC using the SunFire C18 (150 mm × 4,6 mm, 5,0 μm) and gas chromatography with a flame ionization detector using the Rxi-5 ms (30 m long, 0.25 mm outer diameter and 0.25 μm liquid stationary phase thickness). Results. Various chromatographic methods for the routine quantitative analysis of morpholinium thiazotate were developed. The most suitable conditions for sample preparation were established. Proposed methods were compared to find the most ecological and economic. Conclusions. Proposed methods were accurate and reliable. However, an environmental impact assessment showed that GC-FID is a more environmentally friendly and economical method of analysis. Using 12 Principles of green analytical chemistry, the overall “analytical GREEnness (AGREE)” scale for the proposed analytical approach was computed 0.72, showing the good greener nature of the proposed analytical approach

Evaluating the hepatoprotective, ameliorative and antioxidant potentials of the crude aqueous leafy extracts of Mangifera indica plant against acute paracetamol-induced hepatotoxicity in amouse model.

Background:Drug-induced hepatotoxicity is a major public health issue of concern. It significantly affects the development of new pharmaceutical drugs and has led to the withdrawal of many promising pharmaceutical drugs from the pharmaceutical market.Aim:The aim of this study was to evaluate the hepatoprotective, ameliorative and antioxidant effects of the crude aqueous leafy extract of Mangifera indica plant and its different separating medium fractions against acute acetaminophen (paracetamol)-induced hepatotoxicity in a mouse model.Methods & materials:Twelve different groups of six mice (three males and three females) were used for this study. Acetaminophen at a single lethal hepatotoxic dose of 3 g/kg was orally administered on the seventh day to the mice in groups 2 to 12 after their 6-day pretreatment duration for the induction of hepatotoxicity; and were then left for 24 hours before the collection of specimen samples were completed, while group 1 served as control.Results:The crude aqueous leafy extract of M. indica (125-250 mg/kg) produced a dose-dependent reversal of the lethal hepatotoxic effect of oral 3 g/kg dose of paracetamol. At the dose of 250 mg/kg, it significantly (p < 0.0001) reduced the levels of hepatic enzymes markers (alanine transaminase [ALT], aspartate transaminase [AST] and alkaline phosphatase [ALP]) in the serum of treated animals. Also, the effects of the crude aqueous leafy extract were found to be statistically significant (p < 0.0001) more than that of its different separating medium fractional components.Conclusion:The findings from this study demonstrated that the crude aqueous leafy extract of M. indica possesses hepatoprotective effect, possibly mediated through the induction of antioxidant enzymes to prevent the occurrence of oxidative stress damage or most likely through the inhibition of pro-inflammatory mediators which are being induced by the lethal hepatotoxic dose of paracetamol.

Proteomic Analysis of Potential Targets for Non-Response to Infliximab in Patients With Ulcerative Colitis.

Background: Infliximab (IFX) is a potent therapeutic agent used for the treatment of conventional refractory ulcerative colitis (UC). However, the high non-response rate of IFX brings difficulties to clinical applications. In the context of proteomics research, our study of differentially expressed proteins (DEPs) is essential for non-response to IFX in UC patients and provides powerful insights into underlying drug resistance mechanisms. Methods: A total of 12 UC patients were divided into responders to IFX (UCinfG), non-responders to IFX (UCinfL), severe UC (UCsevere) without an IFX treatment history, and mild UC (UCmild) without an IFX treatment history. Subsequently, DEPs were identified from intestinal biopsy tissue between responders and non-responders to IFX by a label-free proteomic quantitative approach, and the general principle of functional protein screening was followed to deduce the potential drug targets and predictors for non-response to IFX in UC patients. Meanwhile, these targets excluded DEPs caused by the severity of inflammation for the first time. The differential expressions of candidate protein targets were validated at the gene sequence level using GEO2R analysis of the GEO database and qRT-PCR in some independent cohorts. Results: A total of 257 DEPs were screened out by mass spectrometry between UCinfG and UCinfL groups, excluding 22 DEPs caused by the severity of inflammation, and compared and verified at the gene sequence level in the Gene Expression Omnibus (GEO) database. Finally, five DEPs, including ACTBL2 (Q562R1), MBL2 (P11226), BPI (P17213), EIF3D (O15371), and CR1 (P17927), were identified as novel drug targets and predictive biomarkers for non-response to IFX. The drug targets were confirmed in the GEO database of the microarray results from three independent cohorts of 70 human intestinal biopsies and validated in qPCR data from 17 colonic mucosal biopsies. Among them, CR1 might affect the activation of the lectin pathway via complement-coated bacteria to play an opsonizing role in inflammation-related pathways closely associated with non-responders to IFX. Conclusion: This is the first report of proteomics analysis for the identification of novel drug targets based on intestinal biopsy tissue, which is significant for hypotheses for mechanistic investigation that are responsible for non-response to IFX and the development of clinical new pharmaceutical drugs.

Increasing the Reuse of Protein Non-Naïve Nonhuman Primates in Pharmaceutical Drug Discovery and Development: An Overview and Industry Position on the Challenges and Benefits.

The IQ Consortium NHP Reuse Working Group (WG) comprises members from 15 pharmaceutical and biotechnology companies. In 2020, the WG developed and distributed a detailed questionnaire on protein non-naïve NHP reuse to the WG member companies. The WG received responses from key stakeholders including principal investigators, facility managers, animal welfare officers and research scientists. This paper's content reflects the consolidated opinion of the WG members and the questionnaire responses on the subject of NHP reuse within nonclinical programs at all stages of research and development. Many of the pharmaceutical companies represented in the working group or participating in the questionnaire have already achieved some level of NHP reuse in their nonclinical programs, but the survey results suggested that there is significant potential to increase NHP reuse further and a need to understand the considerations involved in reuse more clearly. The WG has also focused carefully on the inherent concerns and risks of implementing protein non-naive NHP reuse and has evaluated the best methods of risk assessment and decision-making. This paper presents a discussion on the challenges and opportunities surrounding protein non-naïve NHP reuse and aims to stimulate further industry dialogue on the subject and provide guidance for pharmaceutical companies to establish roadmaps and decision trees enabling increased protein non-naïve NHP reuse. In addition, this paper represents a solid basis for collaborative engagement between pharmaceutical and biotechnology companies with contract research organizations (CROs) to discuss how the availability of protein non-naïve NHP within CROs can be better leveraged for their use within nonclinical studies.

Quantifying the effect of solvent on the morphology of organic crystals using a statistical thermodynamics approach

A method for predicting the effect of solvent on the morphology of organic crystals is presented, providing an efficient screening tool for identifying ideal crystallization solvents. The solvent effect is estimated by the computation of chemical potentials and activity coefficients of crystal surfaces using a first principles-based statistical thermodynamics approach. Density functional theory and COSMO-RS are utilized to determine the activity coefficients of the crystal growth faces of a selection of active pharmaceutical ingredients (APIs) in solvents across a broad range of polarities. The ability of COSMO-RS to predict and quantify the effects of solvent on crystal growth and morphology is assessed using hierarchical clustering to classify the solvents according to their overall interaction strength with the crystal faces. The COSMO-RS approach allows for a physical interpretation of the predictions in terms of surface polarity and is confirmed by comparison to published experimental data. Herein a methodology is reported for automated computation of the activity coefficients of all solvent-surface pairs directly from the drug crystal structure. The procedure goes beyond the traditional trial-and-error solvent selection process and has the potential to be used as a rapid computational screening tool in pharmaceutical drug development.

Solubilization, purification, and ligand binding characterization of G protein-coupled receptor SMO in native membrane bilayer using styrene maleic acid copolymer.

Smoothened (SMO) protein is a member of the G protein-coupled receptor (GPCR) family that is involved in the Hedgehog (Hh) signaling pathway. It is a putative target for treating various cancers, including medulloblastoma and basal cell carcinoma (BCC). Characterizing membrane proteins such as SMO in their native state is highly beneficial for the development of effective pharmaceutical drugs, as their structures and functions are retained to the highest extent in this state. Therefore, although SMO protein is conventionally solubilized in detergent micelles, incorporating the protein in a lipid-based membrane mimic is still required. In this study, we used styrene maleic acid (SMA) copolymer that directly extracted membrane protein and surrounding lipids as well as formed the so-called polymer nanodiscs, to solubilize and purify the SMO transmembrane domain encapsulated by SMA-nanodiscs. The obtained SMA-nanodiscs showed high homogeneity and maintained the physiological activity of SMO protein, thereby enabling the measurement of the dissociation constant (Kd) for SMO ligands SMO-ligands Shh Signaling Antagonist V (SANT-1) and Smoothened Agonist (SAG) using ligand-based solution nuclear magnetic resonance spectroscopy. This work paves the way for investigating the structure, function, and drug development of SMO proteins in a native-like lipid environment.

Location Bias Contributes to Functionally Selective Responses of Biased CXCR3 Agonists to Regulate Inflammation

G Protein‐Coupled Receptors (GPCRs) represent the largest and most diverse family of cell receptors in the human genome and are targeted by ~35% of all FDA‐approved drugs. GPCR signaling is mediated by various effectors, including G proteins, β‐arrestins, and GPCR kinases (GRKs). Recent studies have uncovered that different ligands can bind to the same GPCR and differentially activate specific signaling pathways, a phenomenon known as biased agonism. Most research has focused on characterizing biased agonism at the plasma membrane, but GPCRs are also known to traffic to and signal from a variety of subcellular compartments. To determine if GPCR subcellular localization contributes to biased signaling, we studied how the chemokine family GPCR CXCR3 signals from endosomes following stimulation by the three endogenous ligands CXCL9, CXCL10, and CXCL11.We determined that the biased ligands of CXCR3 promote different amounts of receptor mediated endocytosis and also show markedly different G protein and β‐arrestin signaling profiles at both the plasma membrane and the endosome. The biased activation of G proteins and β‐arrestins promotes differential activation of cytoplasmic and nuclear ERK1/2, as well as cellular transcription in both HEK293 cells and primary CD8+ T‐cells. Inhibition of receptor internalization greatly diminishes the biased signaling observed between the endogenous chemokines. Finally, we demonstrate in a murine model of contact hypersensitivity that receptor internalization is a key component of the ability of a synthetic β‐arrestin biased CXCR3 agonist to potentiate the inflammatory response. The present study shows the CXCR3 biased ligands induce unique signaling profiles at the plasma membrane and the endosome, and that signaling from endosomes greatly contributes to the overall biased responses seen at CXCR3. These results demonstrate that signaling from subcellar compartments is a critical component of GPCR signaling. Our findings have implications in the development of pharmaceutical drugs targeting chemokine receptors and other GPCRs.

Recent Upgradation in Bioanalytical Studies

Analytical methodologies are critical throughout the medicine development process, including marketing and post-marketing studies. The advancement of bio-analytical techniques has resulted in a dynamic field with many exciting potentials for further advancement in the future. Bio-analysis is commonly utilised in the pharmaceutical drug development of drug's and its metabolites' quantitative levels. The goal is to undertake pharmacokinetic and pharmacodynamic studies, as well as kinetics, toxicokinetics, bioequivalence, and exposure studies. Bioanalytical research employs a variety of bioanalytical techniques, including new instrumental techniques, separation techniques, and ligand-Indused test. This study emphasizes the importance of bio-analytical techniques and hyphenated devices in evaluating drug bio-analysis and the role of several current bio-analytical techniques such as LC-Mass, HPLC-PDA, UPLC-Mass spectroscopy, HPTLC, LC-Tandem, AAS, ICP-Mass.etc., and their recent modernization in drug analytical and bio-analysis investigations

PHYTOCHEMICAL SCREENING AND ANTIMICROBIAL SENSITIVITY TEST OF THE AQUEOUS EXTRACT OF THE ROOT WOOD AND ROOT BARK OF Zanthozylum zanthozyloides (LAM.) ON CLINICAL ISOLATES

Zanthozylum zanthozyloides a common component of the rain forest vegetation is used as a chewing stick. It is known for its antioxidative, anti-inflammatory, antisickling, antibacterial, antiviral, antihepatoxicity, antiallegic, antitumor and antihypertensive properties. Phytochemicals present include Saponins, Tannins, Phenols, Cardiac glycoside, Flavonoids, Anthracene and Alkaloids. The aqueous extracts of the root bark and root wood are bactericidal and fungicidal against selected clinical microorganisms such as Staphylococcus epidermidis, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Aspergillus niger, Candida albicans and Rhizopus oryzae. Of all the tested microorganisms Proteus mirabilis was the most sensitive to the root wood extract of Z. zanthozyloides at the concentration of 100mg/ml (18.00 mm), while the least sensitive microorganism was K. pneumoniae at concentration of 12.5mg/ml (1.67 mm). S. epidermidis showed the highest sensitivity of 19.67 mm (100mg/ml) to the extract of the root bark of Z. zanthozyloides while E. coli showed the least sensitivity of 1.67 mm at the concentration of 25mg/ml. Majority of the antimicrobial drugs used in this study were less effective against the tested bacteria and fungi isolates compared to the plant extracts, indicating its relevance in the treatment of infectious diseases. Though the root bark possesses more bioactive materials, the result of this study provides a basis for the development of new pharmaceutical drugs from both root wood, root bark or whole root of Z. zanthozyloides