MODULE 6 - QC 2

Method of analysis: More accurate and precise

Classical/Wet method

Method of analysis: Faster and can analyze trace amounts of analyte

Instrumental

Method of analysis: used for identification and characterization (describing a specific quality or attribute)

Qualitative analyses

Method of analysis: used for measurement and quantification (determining the amount of substance or analyte)

Quantitative analyses

Produces a signal that reflects presence and usually the concentration of the analyte (light source/energy source + sample/chemical system)

Signal generator

The type of signal generated by the interaction of light with sample matter

Analytical signal

Part of the analytical instrument that converts one kind of energy to another. Receives the analytical signal then converts it into an electrical signal that can be processed

Input transducer/detector

Modifies the transduced signal to make it more convenient for the operation of the readout device

Signal processor

Signal is magnified/increased

Amplification

Signal is reduced/decreased

Attenuation

Unwanted noise is removed/reduced from the signal

Filtration

Converts a processed signal to a signal that is understandable by a human operator. Examples: analog meter, digital meter, computer monitor

Readout device

Complete system of energy propagated in a wave form

Electromagnetic spectrum

EM waves: 200-380 nm

UV

EM waves: 380-780 nm

Visible light

EM waves: 200-780 nm

UV-Vis

The electromagnetic spectrum is composed of 2 waves propagated at a ___ angle to each other towards the direction of the light

right angle

Vertical wave in EM spectrum

Electric wave

Horizontal wave in EM spectrum

Magnetic wave

Relationship of frequency and wavelength (direct/indirect)

Indirectly proportional

Velocity of light

3 × 10¹⁰cm/sec

1 micrometer = __ cm

10^-4 cm

1 nm or millimicron = ___ cm

10^-7 cm

1 angstrom = ___ cm

10^-8 cm

1 cps/Hz = ___ ergs

10⁷ ergs

1 electron volt (eV) = _____ J

1.6 × 10¹⁹ J

Planck’s constant

6.62 × 10^-34 Js

Spectroscopic methods: UV-Visible

Absorption

Spectroscopic methods: Fluorometry

Emission

Spectroscopic methods: Turbidimetry

Scattering

Spectroscopic methods: Refractometry

Refraction

Spectroscopic methods: Molecular emission spectroscopy

Emission

Spectroscopic methods: Nephelometry

Scattering

Spectroscopic methods: Atomic absorption spectroscopy

Absorption

Spectroscopic methods: Atomic emission spectroscopy

Emission

Spectroscopic methods: Polarimetry

Rotation

Spectroscopic methods: Nuclear magnetic resonance

Absorption

Spectroscopic methods: X-ray and electron diffraction

Diffraction

Spectroscopic methods: Infrared radiation

Absorption

Chromatographic methods (2)

Gas chromatography, HPLC

Electrochemical methods: Electric potential

Potentiometry

Electrochemical methods: Electric current

Polarography

Electrochemical methods: Electric charge

Coulometry

Miscellaneous methods: Mass-to-charge

Mass spectrometry

Miscellaneous methods: Radioactivity

Radioactive emissions

A general term for the science that deals with the interactions of various types of radiation with matter

Spectroscopy

Refer to the measurement of the intensity of radiation with a photoelectric transducer or other type of electronic device

Spectrometry

A branch of spectrometry which embraces the measurement of the absorption, by chemical species, of radiant energy of definite and narrow wavelength, approximating monochromatic radiation

Spectrophotometry

A branch of spectrometry in which absorption measurement is made in the visible region of the spectrum

Colorimetry

Instruments designed to measure radiant power with the aid of filter, instead of prism or diffraction grating, for the purpose of increasing the sensitivity of the measurement

Colorimeter/Flame photometer

Transition from a lower level to a higher level with transfer of energy from radiation field to an absorber

Absorption

Functional group which absorbs radiant energy in the UV or visible regions of the spectrum

Chromophore

States that the power of transmitted radiant beam increases exponentially as the concentration of the solution containing the absorbing chemical species increases arithmetically

Beer’s law

States that the power of a transmitted radiant beam decreases exponentially as the thickness of the solution containing the absorbing chemical species increases arithmetically

Lambert’s law

When an EMR with an intensity of Io impinges a solution of concentration c and pathlength l, its intensity is diminished in an exponential fashion (I)

Theory of absorptivity

Principle: The electrons in the bonds within the molecule become excited so that they occupy a higher quantum state and, in the process, absorb some of the energy passing through a solution (range 200-700 or 200-780 nm)

UV-Vis spectroscopy

UV-Vis: Source of light for visible light

Tungsten lamp

UV-Vis: Source of light for Ultraviolet

Deuterium, Hydrogen lamp

UV-Vis: Monochromator

Prism/grating

UV-Vis: Cuvette for UV-Vis

Quartz

UV-Vis: Cuvette for visible light only

Optical glass, plastic

Applications of UV-Vis: ____ of drugs in formulations

Quantification

Applications of UV-Vis: Determination of ___ values, ____ and ___ of drugs

pKa, partition coefficient, solubility

Applications of UV-Vis: Part of _____ testing

Dissolution

Applications of UV-Vis: Used in monitoring the reaction kinetics of ____

drug degradation

Applications of UV-Vis: Pharmacopoeial identity checks (___ spectrum)

UV

Summary of UV-Vis applications: IPQD

Identity, pKa-partition coefficient, quantification, dissolution-degradation kinetics

Plot of absorbance readings of the analyte versus the wavelength. Used to determine the wavelength at which maximum absorption occurs (Amax)

Spectral absorbance/Absorbance spectrum

Plot of absorbance values against a series of known solute concentrations. Should yield a straight line. Used to determine the unknown solute concentration

Beer’s plot

Involves measurement of the absorption of EM radiation over the wavenumber range of 4000-400 cm^-1 (2.5-25 um, or 2500-25000nm) caused by promotion of molecules from the ground state of their vibrational modes to an excited vibrational state.

IR-Spectrophotometry

IR: Sample is contained within discs or cells made of alkali metal halides: _____ or _____

KCl or NaCl

IR: 50-1000 um

Far IR

IR: 2.5-50 um

Middle IR

IR: 0.8-2.5 um

Near IR

IR: Makes use of monochromator to select each wavenumber in turn in order to monitor its intensity after the radiation has passed through the sample

Dispersive

IR: Makes use of an interferometer that generates a radiation source in which individual wave numbers can be monitored within 1s pulse radiation without dispersion being required

Fourier transform

IR: Solid sample is prepared by grinding with a mulling agent (mineral oil/Nujol) in a mortar or pestle to a fine paste. The paste is placed on a plate and covered with another.

Mull technique

IR: Solid sample preparation by suspending in KBr pellet and prepared under high pressure

Pellet technique

IR: Solid sample is prepared by cutting into sheets of suitable thickness with a microtome or melted at low heat and allowed to dry as a film.

Film technique

IR: Solid sample is prepared by dissolving in a suitable solvent and used as a liquif sample

Solution technique

IR Applications: Qualitative ___ check for the identity of raw materials and for identifying drugs

Fingerprint

IR Applications: ___ of samples in the solid and semi-solid dosage forms

Characterization

IR Applications: Detection of ___ of drugs

Polymorphs

IR Applications: ____ for films, coatings, and packaging plastics

Fingerprint test

IR Applications Summary: PFC

Polymorphs, fingerprinting, characterization

IR: Region for identification

3-15 um

IR: Group frequency region (4000 to 1500cm-1)

3-8 um

IR: Fingerprint region (1500 to 500 cm-1)

8-15 um

Principle: Metal atoms are volatilized in a flame and their absorption of a narrow bond of radiation produced by a hollow cathode lamp, coated with the particular metal being determined is measured

Atomic absorption spectrophotometer

AAS: Instrument/energy source unique to the AAS for the analysis of metals

Hollow cathode lamp

AAS Applications: Determination of ____ in drugs remaining from the manufacturing process

Metal residues

AAS Applications: Analysis of trace ___ in multivitamin preparations

Minerals

Principle: Radiation in the radiofrequency region is used to excite atoms, usually protons or carbon-13 atoms, so that their spins switch from being aligned with to being aligned against an applied magnetic field.

Nuclear magnetic resonance

NMR Principle summary: NMR

Nuclei 13C and 1H, Magnetic field, Radiofrequency region

NMR Applications: Powerful technique for the characterization of the ___ of raw materials and finished products

Exact molecular structure

NMR Applications: Can determine impurities, including __, without separation down to approximately 10% level

Enantiomeric impurities

Transition from a higher level to a lower level, and the radiation is transferred to the radiation field

Emission

Emission if no radiation is emitted

Nonradioactive decay

Principle Certain molecules, particularly those with a chromophore and a rigid structure, can be excited by a UV/Visible radiation, and will then emit the radiation absorbed at a longer wavelength. The radiation emitted can then be measured. Requires chromophore AND rigid structure.

Molecular emission spectroscopy