Do we need highly sensitive analytical techniques in phase I?

1990 ◽  
Vol 4 (S2) ◽  
pp. 135s-140s
Author(s):  
E. Singlas
Keyword(s):  
Phase I ◽  
Analytical Techniques ◽  
Highly Sensitive

scholarly journals ALTERATION OF HISTONES FROM MOUSE EPIDERMAL CELLS AFTER INCUBATION WITH ELASTASE AND HYALURONIDASE

1971 ◽  
Vol 19 (3) ◽  
pp. 182-185 ◽  
Author(s):  
ALVIN SEGAL ◽  
MARGARET SCHROEDER ◽  
BENJAMIN L. VAN DUUREN
Keyword(s):  
Mouse Liver ◽  
Mouse Skin ◽  
Analytical Techniques ◽  
Epidermal Cells ◽  
Ultraviolet Absorption Spectrum ◽  
Tissue Preparation ◽  
Standard Procedures ◽  
Highly Sensitive ◽  
Mammalian Tissues ◽  
Liver Chromatin

Chromatin was isolated from whole mouse skin, mouse epidermal cells and mouse liver by standard procedures used for isolation of chromatin from other mammalian tissues. Chromatin from whole mouse skin or from mouse epidermal cells had not been isolated or characterized earlier. For the preparation of chromatin from mouse epidermal cells, the latter was separated from dermis by incubation for 30 min at 37°C in a solution containing the enzymes elastase and hyaluronidase. The relative proportions of the chromatin components, the T m and the ultraviolet absorption spectrum were all similar to that of chromatin from whole mouse skin which was not treated with enzymes and to other mammalian chromatin preparations. Electrophoresis of the histones from epidermal chromatin in polyacrylamide gels revealed the absence of histones F1, F3 and F2a2 and the appearance of a new band. Histones isolated from chromatin prepared from the whole mouse skin had a gel electrophoresis pattern virtually identical with histones isolated from mouse liver chromatin and to reported histone patterns from other mammalian tissues. The alterations in mouse epidermal histones are similar to reported changes in histones from calf thymus nucleohistone previously subjected to incubation at various temperatures. The enzymatic incubation technique can therefore not be used as a method of isolating unaltered mouse epidermal chromatin. The findings illustrate that very subtle chemical alterations can be induced by usual methods of tissue preparation and that these changes can only be detected by highly sensitive analytical techniques.

Phase I/II trial of nemorubicin hydrochloride in combination with cisplatin is supported by new preclinical evidences of its mechanism of action

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14116-14116 ◽  
Author(s):  
M. A. Pacciarini ◽  
C. Geroni ◽  
M. A. Sabatino ◽  
M. Ciomei ◽  
O. Valota ◽  
...  
Keyword(s):  
Phase I ◽  
Mechanism Of Action ◽  
Topoisomerase I ◽  
Excision Repair ◽  
Alkylating Agents ◽  
Liver Transaminase ◽  
Highly Sensitive ◽  
Nucleotide Excision ◽  
Combination Studies ◽  
Phase I And Ii

14116 Background: Nemorubicin hydrochloride (nemorubicin) is a non-conventional anthracycline in Phase II evaluation in hepatocellular carcinoma (HCC). Its mechanism of action is not fully elucidated. Although structurally related to doxorubicin, nemorubicin is a topoisomerase I inhibitor, overcomes anthracyclines resistance, is minimally cardiotoxic and is biotransformed by hepatic CYP3A4 into hundred times more cytotoxic metabolite. Phase I and II trials were conducted in Europe and China to test nemorubicin by hepatic intra-arterial (IHA) infusion in HCC patients (pts). The drug was well tolerated up to 600 mcg/m2 q4–6w; DLT was transient liver transaminase elevations. Overall, 57 HCC pts were evaluable for efficacy, with 11/57 confirmed liver CR/PRs (RR = 19.3%; 95% ci 10–31.9%) lasting 1–54+ months. Stable disease ≥ 3 months was observed in 17/57 (29.8%) pts, most with AJCC Stage III, IIIA and IVA. These data supported new trials of nemorubicin in HCC. Methods: To further characterize the mechanism of action of the drug, we generated cells (L1210) resistant to nemorubicin. Since resistant cells were more sensitive than the parental ones to UV irradiation, we reasoned that the nucleotide excision repair (NER) system might be involved in mediating the activity of nemorubicin. To test this hypothesis we used isogenic CHO cells proficient or deficient in excision repair cross-complementing (ERCC) genes, namely ERCC1 and ERCC6 genes. Results: In contrast with what is observed for most DNA damaging drugs that show resistance in the presence of high NER activity, nemorubicin is more cytotoxic in NER proficient than in deficient cells. This suggests that NER pathway plays a role in the cytotoxic effect of nemorubicin. Also, cells resistant to nemorubicin are NER-deficient and are highly sensitive to platinum derivatives and alkylating agents and synergism was found combining cisplatin with nemorubicin. Conclusions: Nemorubicin has a peculiar mechanism of action through the NER system providing the rationale for clinical combination studies with platinum derivatives. A Phase I/II trial of nemorubicin with cisplatin in HCC patients started in Italy at the end of 2005. No significant financial relationships to disclose.

Development and Validation of Novel GC-FID Method for Simultaneous Quantification of Paracetamol and Caffeine in Formulations

2020 ◽  
Vol 42 (4) ◽  
pp. 581-581
Author(s):  
Imtiaz Hussain Imtiaz Hussain ◽  
Yawar Baig Yawar Baig ◽  
Sara Naveed Sara Naveed ◽  
Muhammad Imran Khan Muhammad Imran Khan ◽  
Hafiz Shoaib Sarwar Hafiz Shoaib Sarwar ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Analytical Techniques ◽  
Hplc Method ◽  
Limit Of Quantification ◽  
Simultaneous Quantification ◽  
Ich Guidelines ◽  
Highly Sensitive ◽  
Sensitivity And Selectivity ◽  
Development And Validation ◽  
Accurate Quantification

The advancements in analytical techniques have enabled the development of highly sensitive and accurate methods for the identification of materials up to trace levels using microliter of sample. A highly sensitive and novel GC-FID method has been developed and reported herein for the simultaneous quantification of paracetamol (PCM) and caffeine (CAF) in samples up to trace levels. The method was validated as per ICH guidelines for its sensitivity, linearity, robustness, inter and intra-day variations, limit of quantification (LOQ), limit of detection (LOD), matrix effect, carryover, precision, and accuracy. The LOD of PCM and CAF were determined to be 100 ppm and 10 ppm whereas, LOQ of PCM and CAF were found to be 300 and 30 ppm respectively. The method was applied to quantify PCM and CAF in marketed tablets and dissolution samples of the tablets, which showed highly precise and accurate quantification of PCM and CAF. Moreover, the GC-FID method was compared with reported HPLC method which suggested the superiority of GC-FID method in performance and sensitivity. In short, the newly developed GC-FID method showed sensitivity and selectivity for PCM and CAF estimation and can be adopted as an efficient method for various applications.

scholarly journals Quantitative assessment of organosulfates in size-segregated rural fine aerosol

2009 ◽  
Vol 9 (1) ◽  
pp. 231-238 ◽  
Author(s):  
H. Lukács ◽  
A. Gelencsér ◽  
A. Hoffer ◽  
G. Kiss ◽  
K. Horváth ◽  
...  
Keyword(s):  
Carbonyl Compounds ◽  
Analytical Techniques ◽  
Organic Aerosol ◽  
Water Soluble ◽  
Heterogeneous Reactions ◽  
Smog Chamber ◽  
Organic Film ◽  
Highly Sensitive ◽  
Fine Aerosol ◽  
Mass Concentrations

Abstract. Organosulfates have recently come into the focus of organic aerosol research as potentially important components of water-soluble secondary organic aerosol (SOA) which now dominate tropospheric fine aerosol. Their presence has been confirmed by the identification of sulfate esters of abundant biogenic carbonyl compounds in both smog chamber and continental aerosol. However, none of the studies have been able to determine the mass contribution of organosulfates to SOA. In this paper, as possibly the very first attempt to quantify organosulfates in ambient aerosol, we inferred the mass concentrations of organosulfates by concurrently determining mass concentrations of total sulfur, sulfate and methanesulfonate in rural fine aerosol using two highly sensitive analytical techniques. Although uncertainties were relatively large, we found that mass concentrations of organosulfates in water-soluble fine aerosol ranged from 0.02 μgS m−3 to 0.09 μgS m−3 yielding a mass contribution of 6–12% to bulk sulfur concentrations (or 6–14% to sulfate concentrations). The inferred size distribution of organosulfates suggested that they possibly form in heterogeneous reactions from semi-volatile carbonyl compounds with subsequent or concurrent condensation of gaseous sulfuric acid producing a refractory organic film on particle surfaces.

Highly Sensitive Detection of Inorganic Contamination

2009 ◽  
Vol 145-146 ◽  
pp. 101-104 ◽  
Author(s):  
Burkhard Beckhoff ◽  
Andreas Nutsch ◽  
Roswitha Altmann ◽  
G. Borionetti ◽  
C. Pello ◽  
...  
Keyword(s):  
Detection Limits ◽  
Analytical Techniques ◽  
Total Reflection ◽  
Inorganic Contaminants ◽  
Research Activity ◽  
Joint Research ◽  
X Ray ◽  
Low Concentration ◽  
Highly Sensitive ◽  
Highly Sensitive Detection

As the detection of inorganic contaminants is of steadily increasing importance for the improvement of yields in microelectronic applications, the aim of one of the joint research activity within the European Integrated Activity of Excellence and Networking for Nano- and Micro-Electronics Analysis (ANNA, site: www.ANNA-i3.org) is the development and assessment of new methodolo¬gies and metrologies for the detection of low concentration inorganic contaminants in silicon and in novel materials. A main objective consist in the benchmarking of various analytical techniques avail¬able in the laboratories of the participating ANNA partners, including the improvement of the res¬pective detection limits as well as the quantitation reliablity of selected analytical techniques such as total-reflection x-ray fluorescence (TXRF) analysis.

scholarly journals Quantitative assessment of organosulfates in size-segregated rural fine aerosol

2008 ◽  
Vol 8 (2) ◽  
pp. 6825-6843
Author(s):  
H. Lukács ◽  
A. Gelencsér ◽  
A. Hoffer ◽  
G. Kiss ◽  
K. Horváth ◽  
...  
Keyword(s):  
Carbonyl Compounds ◽  
Analytical Techniques ◽  
Organic Aerosol ◽  
Water Soluble ◽  
Heterogeneous Reactions ◽  
Smog Chamber ◽  
Organic Film ◽  
Highly Sensitive ◽  
Fine Aerosol ◽  
Mass Concentrations

Abstract. Organosulfates have recently come into the focus of organic aerosol research as potentially important components of water-soluble secondary organic aerosol (SOA) which now dominate tropospheric fine aerosol. Their presence has been confirmed by the identification of sulfate esters of abundant biogenic carbonyl compounds in both smog chamber and continental aerosol. However, none of the studies have been able to determine the mass contribution of organosulfates to SOA. In this paper, as possibly the very first attempt to quantify organosulfates in ambient aerosol, we inferred the mass concentrations of organosulfates by concurrently determining mass concentrations of total sulfur, sulfate and methanesulfonate in rural fine aerosol using two highly sensitive analytical techniques. Although uncertainties were relatively large, we found that mass concentrations of organosulfates in water-soluble fine aerosol ranged from 0.02 μgS m−3 to 0.09 μgS m−3 yielding a mass contribution of 6–12% to bulk sulfur concentrations (or 6–14% to sulfate concentrations). The inferred size distribution of organosulfates suggested that they possibly form in heterogeneous reactions from semi-volatile carbonyl compounds with subsequent or concurrent condensation of gaseous sulfuric acid producing a refractory organic film on particle surfaces.

Recent Advances in Biosensors Based Nanostructure for Pharmaceutical Analysis

2019 ◽  
Vol 15 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Eslam Pourbasheer ◽  
Zhila Azari ◽  
Mohammad Reza Ganjali
Keyword(s):  
Sample Preparation ◽  
Real Time ◽  
High Frequency ◽  
Pharmaceutical Analysis ◽  
Analytical Techniques ◽  
Recent Advances ◽  
Highly Sensitive ◽  
Frequency Monitoring ◽  
Rapid Quantification

Background: The development of novel nanostructures for pharmaceutical analysis has received great attention. Biosensors are a class of analytical techniques competent in the rapid quantification of drugs. Recently, the nanostructures have been applied for modification of biosensors. Objective: The goal of the present study is to review novel nanostructures for pharmaceutical analysis by biosensors. Method: In this review, the application of different biosensors was extensively discussed. Results: Biosensors based nanostructures are a powerful alternative to conventional analytical techniques, enabling highly sensitive, real-time, and high-frequency monitoring of drugs without extensive sample preparation. Several examples of their application have been reported. Conclusion: The present paper reviews the recent advances on the pharmaceutical analysis of biosensor based nanostructures.

On Stability Analysis and Parametric Design of Supply Networks Under the Presence of Transportation Delays

2006 ◽  
Author(s):  
Rifat Sipahi ◽  
Stefan Lammer ◽  
Dirk Helbing ◽  
Silviu-Iulian Niculescu
Keyword(s):  
Stability Analysis ◽  
Parametric Design ◽  
Analytical Techniques ◽  
Bullwhip Effect ◽  
Supply Network ◽  
Supply Networks ◽  
Stable Regime ◽  
Highly Sensitive ◽  
And Mathematics ◽  
Underlying Mechanisms

Management of interconnected manufacturing units, supply networks, constitutes a timely, but challenging problem in Physics, Operations Research and Mathematics, as it carries very rich dynamics. At the first stage, a very well understanding of the underlying mechanisms and interactions within the hierarchical construct of such networks is required. For this pursuit, a more realistic approach is proposed in this paper, which takes into account the presence of naturally existing transportation delays of supplies in between individual production units. In general, the presence of delays in the dynamics imports another source of instability, which needs to be addressed. However, it is well-known that a thorough stability analysis against delays carries complications, thus it is non-trivial. We present analytical techniques to tackle such difficulties, surfacing allowable transportation delays within the supply network that guarantees stable stock levels. This, in parallel, enables the selection of production rates assuring the supply network to operate in a stable regime. Moreover, we show that under certain parametric settings, the supply network dynamics may become highly sensitive against the presence of delays, which in turn, initiates an undesirable phenomenon called bullwhip effect. We present case studies demonstrating the bullwhip effect and suggesting parametric selections to avoid this undesired behavior within supply networks.

scholarly journals Tuning the aggregation behavior of pH-responsive micelles by copolymerization

2015 ◽  
Vol 6 (14) ◽  
pp. 2761-2768 ◽  
Author(s):  
Daniel B. Wright ◽  
Joseph P. Patterson ◽  
Anaïs Pitto-Barry ◽  
Pepa Cotanda ◽  
Christophe Chassenieux ◽  
...  
Keyword(s):  
Diblock Copolymers ◽  
Analytical Techniques ◽  
Ph Sensitive ◽  
Aggregation Behavior ◽  
Ph Responsive ◽  
Highly Sensitive ◽  
Amphiphilic Diblock Copolymers ◽  
Sensitive Behavior

A series of pH sensitive amphiphilic diblock copolymers where the associating block is a copolymer have been synthesized. Their pH sensitive behavior has been explored by a range of analytical techniques and the nanostructures formed are highly sensitive to both pH and the associating block composition.

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