Pharmaceutical Quality Control
Comprehensive Interview Questions & Answers for Written Exams and Viva Voce
UV/Vis spectroscopy is routinely used in analytical chemistry for the quantitative determination of different analytes, such as transition metal ions, highly conjugated organic compounds, and biological macromolecules.
There are two regions in UV.
(i) Vacuum UV region: Below \(200\mathrm{nm}\)
(ii) Ordinary UV region: \(200 - 400\mathrm{nm}\)
IR spectroscopy (which is short for infrared spectroscopy) deals with the infrared region of the electromagnetic spectrum, i.e. light having a longer wavelength and a lower frequency than visible light. Infrared Spectroscopy generally refers to the analysis of the interaction of a molecule with infrared light.
1. UV/Electronic spectroscopy:
Promotion of e- from the ground state to the higher energy state
Vacuum UV region \(< 200\mathrm{nm}\)
UV region \(200\sim 400\mathrm{nm}\)
VIS region \(400\sim 800\mathrm{nm}\)
2. IR spectroscopy:
Near IR region \(800\sim 2500\mathrm{nm}\)
Mid IR/IR region \(2500\sim 15000\mathrm{nm}\) \(4000\mathrm{cm}^{-1}\sim 667\mathrm{cm}^{-1}\) (wave number)
Far IR region \(15000\sim 25000\mathrm{nm}\)
Finger print region \(>6666.7\mathrm{nm}\) less than \(1500\mathrm{cm}^{-1}\) (wave number) Absorption at higher wavelength in the IR region
3. NMR spectroscopy:
Radiation of the longest wavelength range --- radio waves --- 60-300 MHz
Ionic bonds result from the mutual attraction between oppositely charged ions while a covalent bond is a bond that results from a sharing of electrons between nuclei. They tend to be stronger than covalent bonds due to the columbic attraction between ions of opposite charges.
The functional group is defined as an atom or a group of atoms joined in a specific manner, which gives the chemical properties of the organic compound and are the centers for chemical reactivity. Compounds having a similar functional group have undergone similar reactions.
Bond dissociation energy is the minimum amount energy required to break a single bond. The greater is the bond dissociation energy, the more stable is the compound.
In methane, a carbon atom is bonded to 4 hydrogen atoms and has no lone pairs. With 4 bonding sites, it will have a hybridization of \(\mathrm{SP}^3\) with a tetrahedral shape.
We know carbon is tetravalent and hydrogen is monovalent. Thus, after formation of \(\mathrm{CH}_4\) molecule it have 4 sigma or bond pairs \((bp)\) and 0 lone pair \((lp)\) or pi bond. Thus its hybridization is sp3 and its bond angle is 109.5 degrees.
A water molecule consists of two hydrogen atoms bonded to an oxygen atom, and its overall structure is bent. This is because the oxygen atom, in addition to forming bonds with the hydrogen atoms, also carries two pairs of unshared \((lp)\) electrons.
Water has 8 electrons around the central oxygen atom. This means there are four electron pairs arranged in a tetrahedral shape. There are two bonding pairs and two lone pairs. The resulting shape is bent with an H-O-H angle of \(104.5^{\circ}\).
Water has hydrogen bonds, dipole-induced dipole forces, and London dispersion forces.
Actually, water has all three types of intermolecular forces, with the strongest being hydrogen bonding.
All things have London dispersion forces - the weakest interactions being temporary dipoles that form by shifting of electrons within a molecule.
Water, having hydrogen bound to an oxygen atom (which is much more electronegative than hydrogen, thus not sharing those bonded electrons very nicely) form dipoles of a special type called hydrogen bonds.
[The London dispersion force is the weakest intermolecular force. The London dispersion force is a temporary attractive force that results when the electrons in two adjacent atoms occupy positions that make the atoms form temporary dipoles. This force is sometimes called an induced dipole-induced dipole attraction. London forces are the attractive forces that cause nonpolar substances to condense to liquids and to freeze into solids when the temperature is lowered sufficiently.]
Van der Waals forces include attractions and repulsions between atoms, molecules, and surfaces, as well as other intermolecular forces. They differ from covalent and ionic bonding in that they are caused by correlations in the fluctuating polarizations of nearby particles (a consequence of quantum dynamics).
Lewis Acid: a species that accepts an electron pair (i.e., an electrophile) and will have vacant orbitals.
Lewis Base: a species that donates an electron pair (i.e., a nucleophile) and will have lone-pair electrons.
pH is a measure of hydrogen ion concentration, a measure of the acidity or alkalinity of a solution. The pH scale usually ranges from 0 to 14. Aqueous solutions at \(25^{\circ}C\) with a pH less than 7 are acidic, while those with a pH greater than 7 are basic or alkaline.
A buffer solution (more precisely, pH buffer or hydrogen ion buffer) is an aqueous solution consisting of a mixture of a weak acid and its conjugate base, or vice versa. Its pH changes very little when a small amount of strong acid or base is added to it.
The Arrhenius acid-base concept classifies a substance as an acid if it produces hydrogen ions \(\mathrm{(H^{+})}\) or hydronium ions in water. A substance is classified as a base if it produces hydroxide ions \(\mathrm{(OH^{-})}\) in water.
A Bronsted-Lowry acid is a chemical species that donates one or more hydrogen ions in a reaction. In contrast, a Bronsted-Lowry base accepts hydrogen ions. When an acid donates its proton, the acid becomes its conjugate base and when a base accepts proton, the base becomes its conjugate acid.
A more general look at the theory is as an acid as a proton donor and a base as a proton acceptor.
118 elements have been identified: the first 94 occur naturally on Earth, and the remaining 24 are synthetic elements. There are 80 elements that have at least one stable isotope and 38 that have exclusively radionuclides, which decay over time into other elements. Iron is the most abundant element (by mass) making up Earth, while oxygen is the most common element in the Earth's crust.
S-block elements are the elements found in Group 1 and Group 2 on the periodic table. Group 1 is the alkali metals which have one valence electron. They have low ionization energies which makes them very reactive. Group 2 is the alkali earth metals which have two valence electrons, filling their s sublevel.
Oxidation occurs when there is addition of oxygen or removal of hydrogen or removal of electrons. The substance which oxidizes other substance is called oxidizing agent.
Reduction occurs when there is addition of hydrogen or removal of oxygen or addition of electrons. The substance which reduces other substance is called reducing agent.
When reduction and oxidation occurs simultaneously it is called redox reaction.
Ionization energy is the energy required to remove an electron from a gaseous atom or ion. The first or initial ionization energy or Ei of an atom or molecule is the energy required to remove one mole of electrons from one mole of isolated gaseous atoms or ions.
Ionization energy exhibits periodicity on the periodic table. The general trend is for ionization energy to increase moving from left to right across an element period. Moving left to right across a period, atomic radius decreases, so electrons are more attracted to the (closer) nucleus.
The shielding effect is when the electron and the nucleus in an atom have a decrease in attraction which changes the nuclear charge. An example of shielding effect is in nuclear fission when electrons furthest from the center of the atom are pulled away.
Shielding effect is the reduction in the effective nuclear charge on the electron cloud, due to differences in the attraction forces between electrons and the nucleus. Shielding effect is also known as the Screening Effect.
Atomic radius patterns are observed throughout the periodic table. Atomic size gradually decreases from left to right across a period of elements. This is because, within a period or family of elements, all electrons are added to the same shell.
In chemistry, a radical is an atom, molecule, or ion that has an unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spontaneously dimerize. Most organic radicals have short lifetimes.
The s-block of elements is the alkali metals and the alkaline earth metals. The d-block of elements is the transition metals. The f-block of elements is the lanthanides (first row) and the actinides (second row).
The p-block elements are unified by the fact that their valence electrons (outermost electrons) are in the p orbital.
The elements which have partially filled d-orbitals either ground state or in one or more of their ions, are called d-block elements or outer transition elements. Their properties are intermediate between s-block elements and p-block elements.
The f block elements are the lanthanides and actinides and are called the inner transition elements because of their placement in the periodic table due to their electron configurations. The f orbitals of the electron shell are filled with "n-2." Total 28 atoms are.
In chemistry and atomic physics, the electron affinity of an atom or molecule is defined as the amount of energy released or spent when an electron is added to a neutral atom or molecule in the gaseous state to form a negative ion.
Electron affinity increases upward for the groups and from left to right across periods of a periodic table because the electrons added to energy levels become closer to the nucleus, thus a stronger attraction between the nucleus and its electrons.
A titration is a technique where a solution of known concentration (titrant) is used to determine the concentration of an unknown solution (titrand). Typically, the titrant is added from a burette to a known quantity of the analyte (the unknown solution) until the reaction is complete.
A primary standard is a reagent that is extremely pure, stable, it not a hydrate/has no water of hydration, and has a high molecular weight.
Example: \(\mathrm{CaCO_3}\), \(\mathrm{Na_2CO_3}\), \(\mathrm{Na_2SO_4}\), \(\mathrm{Na_2C_2O_4}\), \(\mathrm{NaCl}\), \(\mathrm{AgNO_3}\), \(\mathrm{K_2Cr_2O_7}\), \(\mathrm{As_2O_3}\), Oxalic acid, Benzoic acid, KBr, Potassium hydrogen phthalate, Sulfanilic acid, Zn, Mg, Ni etc.
A secondary standard is a standard that is prepared in the laboratory for a specific analysis. It is usually standardized against a primary standard.
Example: \(\mathrm{KMnO_4}\), \(\mathrm{NaOH}\), \(\mathrm{KOH}\), \(\mathrm{HCl}\), \(\mathrm{H_2SO_4}\) etc.
Thin-layer chromatography (TLC) is a chromatography technique used to separate nonvolatile mixtures. Thin-layer chromatography is performed on a sheet of glass, plastic, or aluminium foil, which is coated with a thin layer of adsorbent material, usually silica gel, aluminium oxide (alumina), or cellulose. This layer of adsorbent is known as the stationary phase.
Chromatography is a technique to separate mixtures of substances into their components on the basis of their molecular structure and molecular composition.
This involves a stationary phase (a solid, or a liquid supported on a solid) and a mobile phase (a liquid or a gas). The mobile phase flows through the stationary phase and carries the components of the mixture with it. Sample components that display stronger interactions with the stationary phase will move more slowly through the column than components with weaker interactions. This difference in rates causes the separation of various components.
High Performance Liquid Chromatography (HPLC) is a form of column chromatography that pumps a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase).
Mobile phase is the liquid or gas that flows through a chromatography system, moving the materials to be separated at different rates over the stationary phase.
Stationary phase is the solid or liquid phase of a chromatography system on which the materials are to be separated or selectively adsorbed.
Column is the stationary phase in HPLC.
Chromatography works on the principle that different compounds will have different solubility and adsorption to the two phases between which they are to be partitioned. Thin Layer Chromatography (TLC) is a solid-liquid technique in which the two phases are a solid (stationary phase) and a liquid (moving phase).
Potentiometric titration is a volumetric method in which the potential between two electrodes is measured (referent and indicator electrode) as a function of the added reagent volume.
Types of potentiometric titrations for the determination of analytes in photo processing solutions include acid-base, redox, precipitation, and complexometric.
Isomers are molecules with the same chemical formula but different chemical structures. That is, isomers contain the same number of atoms of each element, but have different arrangements of their atoms in space.
Two molecules are described as stereoisomers if they are made of the same atoms connected in the same sequence, but differ in the three-dimensional orientations of their atoms in space.
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other but non-superposable (not identical), much as one's left and right hands are mirror images of each other that cannot appear identical simply by reorientation.
D-alanine and L-alanine are examples of enantiomers or mirror images. Only the L-forms of amino acids are used to make proteins.
An asymmetric carbon atom (chiral carbon) is a carbon atom that is attached to four different types of atoms or groups of atoms.
Enantiomers have identical chemical and physical properties in an achiral environment. Enantiomers rotate the direction of plane polarized light to equal, but to opposite angles and interact with other chiral molecules differently.
Diastereomers are stereoisomers that are not mirror images of one another and are non-superimposable on one another.
An electrolyte is a substance that produces an electrically conducting solution when dissolved in a polar solvent, such as water. The dissolved electrolyte separates into cations and anions, which disperse uniformly through the solvent. Electrically, such a solution is neutral.
A solvent is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. The quantity of a solute that can be dissolved in a specific volume of solvent varies with temperature.
Organic solvent: Chloroform, Acetone, Ethanol, Methanol, etc.
Inorganic solvent: Water, Ammonia, Carbon dioxide, Carbon tetrachloride, Hydrogen fluoride, Molten salt, Sulfuric acid, etc.
Hard water contains a noticeable amount of dissolved minerals, namely calcium and magnesium, but also chalk and lime.
Soft water is treated water that only contains sodium.
For many solids dissolved in liquid water, the solubility increases with temperature. The increase in kinetic energy that comes with higher temperatures allows the solvent molecules to more effectively break apart the solute molecules that are held together by intermolecular attractions.
Leveling effect or solvent leveling refers to the effect of solvent on the properties of acids and bases. The strength of a strong acid is limited ("leveled") by the basicity of the solvent. Similarly the strength of a strong base is leveled by the acidity of the solvent.
Common uses for organic solvents are in dry cleaning (e.g. tetrachloroethylene), as paint thinners (e.g. toluene, turpentine), as nail polish removers and glue solvents (acetone, methyl acetate, ethyl acetate), in spot removers (e.g. hexane, petrol ether), in detergents (citrus terpenes) and in perfumes (ethanol).
Polar solvents have large dipole moments (aka "partial charges"); they contain bonds between atoms with very different electronegativity, such as oxygen and hydrogen.
Non polar solvents contain bonds between atoms with similar electronegativity, such as carbon and hydrogen (think hydrocarbons, such as gasoline).
Non-polar solvents are lipophilic as they dissolve non-polar substances such as oils, fats, greases.
Examples: carbon tetrachloride \((\mathrm{CCl}_4)\), pentane, toluene, benzene \((\mathrm{C}_6\mathrm{H}_6)\), and diethyl ether \((\mathrm{CH}_3\mathrm{CH}_2\mathrm{OCH}_2\mathrm{CH}_3)\), hexane \((\mathrm{CH}_3(\mathrm{CH}_2)_4\mathrm{CH}_3)\), methylene chloride \((\mathrm{CH}_2\mathrm{Cl}_2)\).
A polar solvent is a liquid with molecules that have a slight electrical charge due to its shape.
Example: water, deuterium oxide (heavy water for NMR), ethanol, methanol, acetone, methyl ethyl ketone, isopropanol, n-propanol, acetonitrile, DMSO (dimethyl sulfoxide) or deuterated DMSO (heavy DMSO for NMR), DMF (dimethyl formamide);
HPLC relies on pumps to pass a pressurized liquid and a sample mixture through a column filled with adsorbent, leading to the separation of the sample components. The active component of the column, the adsorbent, is typically a granular material made of solid particles (e.g., silica, polymers, etc.), 2-50μm in size.
There are following variants of HPLC, depending upon the phase system (stationary) in the process:
1. Normal Phase HPLC
This method separates analytes on the basis of polarity. NP-HPLC uses polar stationary phase and non-polar mobile phase. Therefore, the stationary phase is usually silica and typical mobile phases are hexane, methylene chloride, chloroform, diethyl ether, and mixtures of these. Polar samples are thus retained on the polar surface of the column packing longer than less polar materials.
2. Reverse Phase HPLC
The stationary phase is nonpolar (hydrophobic) in nature, while the mobile phase is a polar liquid, such as mixtures of water and methanol or acetonitrile. It works on the principle of hydrophobic interactions hence the more nonpolar the material is, the longer it will be retained.
3. Size-exclusion HPLC
The column is filled with material having precisely controlled pore sizes, and the particles are separated according to it's their molecular size. Larger molecules are rapidly washed through the column; smaller molecules penetrate inside the porous of the packing particles and elute later.
4. Ion-Exchange HPLC
The stationary phase has an ionically charged surface of opposite charge to the sample ions. This technique is used almost exclusively with ionic or ionizable samples. The stronger the charge on the sample, the stronger it will be attracted to the ionic surface and thus, the longer it will take to elute. The mobile phase is an aqueous buffer, where both pH and ionic strength are used to control elution time.