Introduction& Principle of Buffering
Buffer capacity
Types of Buffer
Henderson-Hesselbalch equation
Mechanism of Buffer action
Buffer system in body
Disturbance of Buffer balancing
Buffer Titration & curve
Application of Buffer
Conclusion
References
Resent reaserches
Introduction& Principle of Buffering
Buffer capacity
Types of Buffer
Henderson-Hesselbalch equation
Mechanism of Buffer action
Buffer system in body
Disturbance of Buffer balancing
Buffer Titration & curve
Application of Buffer
Conclusion
References
Resent reaserches
Maintenance of pH of body fluids and its disorders for undergraduate medical students and postgraduate students in medicine, paediatrics, respiratory medicine etc
A poor solubility in water limits in a drastic way the effi cacy of a drug, because the absorption phenomenon requires the drugs be in dissolution. The therapeutic activity of a drug is depending of its acid-base dissociation constant (pKa) and solubility, the knowledge of pKa values being thus of great worth. The solubility method can be very useful in spite of their limitations if an appropriate method is available to carry out the solubility measurements of scarce solubility compounds. Some examples taken from the bibliography whose behaviour is well adapted to conventional acid-base dissociation equilibria without further complications are selected for study: Calcein blue, butaperazine, sulfadiazine, tyrosine, 8-hydroxiquinoleine and nifl umic acid. The pKa values have been recalculated applying the single least squares method and the classic monoprotic acid bilogarithmic model. A slope-intercept procedure is also applied to get the evaluation of acidity constants of overlapping equilibria (pKa2 and pKa3 of tyrosine). Results obtained in all cases are compared with literature data.
NDSRIs - Nitrosamine Drug Substance-Related Impurities (NDSRIs)Chandra Prakash Singh
NDSRIs impurities share structural similarity to the API (having the API or API fragment in the chemical structure) and are therefore unique to each API.
NDSRIs generally form in the drug product through nitrosation of APIs (or API fragments) that have secondary or tertiary amines when exposed to nitrosating agents such as residual nitrites in excipients used to formulate the drug product.
Generally, the presence of high levels of NDSRIs has been associated with drug products rather than APIs because NDSRI formation usually results from a reaction between the API or API fragment and nitrosating agents in the drug formulation.
However, NDSRIs can potentially form in APIs when nitrosating agents are present in the API manufacturing process or when APIs undergo processing steps that can potentially induce their formation such as fluid bed drying at an elevated temperature and jet milling because these can create favorable conditions in which nitrogen oxides can react with at-risk APIs.
NDSRIs often lack carcinogenicity and mutagenicity study data (typically from animal studies) from which an AI limit can be determined.
This guidance provides a recommended methodology for AI limit determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can apply, in the absence of other FDA recommended AI limits, in their evaluations of approved and marketed drug products as well as products in development or under review by FDA.
Currently Identified Risk Factors for Presence of Nitrosamines.pptxChandra Prakash Singh
N-Nitrosamines can be formed when an amine and nitrosating agent are combined under favourable conditions although other generation pathways are also possible, such as e.g. oxidation and reduction processes from hydrazine-type compounds and N-nitro derivatives.
Root causes for N-nitrosamines in medicinal products identified to date can be grouped as risk factors linked exclusively with the manufacturing process and storage of active substance and/or as risk factors associated with manufacture and storage of the finished product.
Moreover, there are risk factors specifically linked to GMP aspects.
Basic Understanding of LCMS
Ion Optics Path and Parameters.
Mass spectrometry measures the mass-to-charge ratio of ions to identify unknown compounds, to quantify known compounds, and to provide information about the structural and chemical properties of molecules.
The mass spectrometer has a series of quadrupole filters that transmit ions according to their mass-to-charge (m/z) ratio.
When the energy of the accelerated electrons is higher than a certain threshold value (which depends on the metal anode), a second type of spectrum is obtained superimposed on top of the white radiation. It is called the characteristic radiation and is composed of discrete peaks.
The energy (and wavelength) of the peaks depends solely on the metal used for the target and is due to the ejection of an electron from one of the inner electron shells of the metal atom.
This results in an electron from a higher atomic level dropping to the vacant level with the emission of an X-ray photon characterised by the difference in energy between the two levels.
CHARACTERIZATION OF CRYSTALLINE AND PARTIALLY CRYSTALLINE SOLIDS BY X-RAY POWDER DIFFRACTION (XRPD)
USP <941>
Every crystalline phase of a given substance produces a characteristic X-ray diffraction pattern.
Diffraction patterns can be obtained from a randomly oriented crystalline powder composed of crystallites (crystalline regions within a particle) or crystal fragments of finite size.
Essentially three types of information can be derived from a powder diffraction pattern:
The angular position of diffraction lines (depending on geometry and size of the unit cell).
The intensities of diffraction lines (depending mainly on atom type and arrangement and preferred orientation within the sample.
Diffraction line profiles (depending on instrumental resolution, crystallite size, strain, and specimen thickness).
LCMS - Ion Optics Path and Parameters
Source and gas parameters: These parameters can change depending on the ion source used.
Compound parameters: These parameters consist mostly of voltages in the ion path. Optimal values for compound-dependent parameters vary depending on the compound being analyzed.
Resolution parameters: These parameters affect the resolution and calibration.
Detector parameters: These parameters affect the detector.
A divert valve allows you to switch portions of the mobile phase to waste before the mass spectrometer.
This is particularly important for the portion containing all the un-retained components – many of which are likely to be involatile and contaminate the source. If you really want to keep things clean use a divert valve to divert everything to waste except the compounds of interest.
The integrated diverter valve, which is located next to the ion source, can be plumbed in injector mode or diverter mode.
LCMS Interface
API techniques (ESI, APCI and APPI)
In LCMS, ions can be generated through either the continuous or pulsed (discontinuous) modes.
The three API techniques (ESI, APCI and APPI) that were introduced operates in the continuous mode, giving a constant flow/supply of ions to the MS.
On the other hand, the pulsed mode generates a discontinuous source of ions such as the Matrix-Assisted Laser Desorption/Ionization (MALDI).
Analytical control strategy - Part -4 : How the ACS Applies to the Product Lifecycle and How the modern concept of a lifecycle model can be applied to analytical procedures.
How the modern concept of a lifecycle model, which is based on process validation and described in ICH guidelines Q8, Q9, and Q10, can be applied to analytical procedures.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
2. ACID–BASE EQUILIBRIA AND REVERSED-PHASE RETENTION
Uncharged
molecule
Acid (HA)
Base (B)
Charged
molecule
Acid (A− )
Base (BH+)
(Acids) HA ⇔ A− + H+
(Bases) B + H+ ⇔ BH+
Ionization
Hydrophobic
Less Polar
More retained in RPC
Hydrophilic
More polar
Less retained in RPC
As a result its retention factor k in RPC can be reduced 10-fold or more
3. Acids
HA ⇔ A− + H+
Bases
B + H+ ⇔ BH+
When the mobile-phase
pH is increased
When mobile-phase pH
decreases
Bases gain a proton
and become ionized
Acids lose a proton and
become ionized
Acid Bases
(Acids) Ka = [A−][H+]
[HA]
(Bases) Ka = [B][H+]
[BH+]
Acidity constant Ka
𝑨𝑪𝑰𝑫 𝑷 𝑲𝒂 = 𝒑𝑯 − 𝐥𝐨𝐠
𝑨−
𝑯𝑨
𝑩𝑨𝑺𝑬𝑺 𝑷 𝑲𝒂 = 𝒑𝑯 − 𝐥𝐨𝐠
𝑩
𝑩𝑯 +
Henderson–Hasselbalch equation
pKa value = −logKa
ACID–BASE EQUILIBRIA AND REVERSED-PHASE RETENTION
4. Hypothetical illustration of the RPC separation of an acidic compound HA from a basic compound B as a function of pH.
Ionization of HA and B as a function of
mobile-phase pH and effect on k.
Sample separation as a function of mobile-
phase pH.
5. Section - I
Reproducible
Section -II
Less reproducible
Section - III
Reproducible
The mobile-phase pH - In order to control selectivity and resolution.
Section -II
A change in pH will provide a maximum change in
retention and separation.
Chosen if we want to change selectivity and
resolution by varying pH.
When an acid or base is half-ionized
A change in pH of 0.1 unit.
Will result in a change of k by about 10%
Can result in a change in resolution of
as much as ±2.5Rs units.
A possible change in separation from baseline
resolution (Rs >1.5) to complete overlap (Rs = 0).
6. Effect of mobile-phase pH on RPC retention as a function of solute type.
Sample: 1, salicylic acid; 2, Phenobartitone; 3, Phenacetin; 4, Nicotine; 5, Methylamphetamine
Compounds 2 and 4 are
seen to have pKa
values of about 8 and
6.5, respectively.
Compounds whose retention
increases significantly as pH
increases are bases (4 and 5).
The shape of a plot of retention versus pH for a peak allows a determination of its sample type (acid, base, or neutral), and a
rough estimate of its pKa value.
Compounds whose
retention decreases with an
increase in pH are acids
(1 and 2).
Compounds that show little
change in retention with pH
(3) are either neutral or are
fully ionized over the pH
range studied.
While the pKa values of
compounds 1 and 5
cannot be estimated
accurately (a complete
retention vs. pH curve is
required), it is safe to say
that pKa ≥ 9 for
compound 5, and pKa ≤ 3
for compound 1.
7. A change in mobile-phase pH can be a powerful means of controlling relative retention (selectivity) and
separation for samples that contain acids and/or bases.
This sample contains acids and bases with a wide range in pKa values and therefore exhibits sizable changes
in retention for small changes in pH throughout the range 3 < pH < 9. Consequently, either a careful control
of mobile pH will be required for the separation of this sample or conditions must be selected that provide
excess resolution (Rs 2).
In order to avoid pH-related variations in retention, the mobile-phase pH can be selected to be different from
the pKa values of all sample components, by at least ±1.5 pH-units (regions I and III of Fig).
As the majority of compounds have pKa values >4, low-pH separations (2 ≤ pH ≤ 3) are more likely to be less
sensitive to small changes in pH—which is one reason for beginning method development with a low-pH
mobile phase.
ACID–BASE EQUILIBRIA AND REVERSED-PHASE RETENTION
8. if a solute is half-ionized, a change in mobile-phase pH by 0.1 unit can cause a complete loss of resolution. This
suggests that mobile-phase pH may need to be controlled within about 0.02 units for such a separation, which
could prove difficult for many laboratories.
Values of pKa in the literature for different acids or bases usually refer to solutions in buffered-water at near-
ambient temperatures. If the mobile phase contains organic solute, or if the temperature is much different from
ambient, values of both pH and pKa can change significantly.
Thanks
ACID–BASE EQUILIBRIA AND REVERSED-PHASE RETENTION