Pre lec 1- drug analysis Flashcards
Raw Material Specifications- MPT
- A useful non-specific check on purity
Raw Material Specification- Loss of drying
- Often done at 150’C
- Reveals
- Residual solvents from manufacture
- Moisture
- Ensures that the correct hydrate is present (loss of water of crystalisation; effect mpt)
Impurities- Synthesis
- Starting materials, reagents, solvents, byproducts
- Processing plant
- Heavy metals from soldered joints
- Iron from steel vessels
Impurities- Limits depends upon
- Toxicity
- Feasibility
- Pharmacopoeias simply have a qualitative limit test for impurities rather than individual determinations
Impurities- Regulated substances
- Specific synthetic pre-cursors, byprodu cts, degradation products chemically related to the drug
- TLC, HPLC
Impurities- Assay
- Gives the amount of drug present in the sample
- Gives the amount of total impurities present in the sample
Does a sample of raw material conform to reference- a common question in the industry
- An in house monograph would probably contain
- NMR (Proton + sometimes C-13)
- IR
- UV
- MS
- Apperance
- MP (Melting range under defined conditions)
An in-house monograph would probably contain
- Elemental analysis- sometimes (timescale)
- Loss of weight on drying
- Quantitative TLC (Identity + purity by comparison with reference and known impurities)
- HPLC- An assay against reference material of known purity
- Determines drug content
- Quantifies known impurities for which there are reference samples e.g. manufacturing by-products
Example: Synthesis of metronidazole
List of test for inclusion in metronidazole specification
- Solubility
- Appearance
- Identification test (IR, UV co-elution on TLC etc) on the drug itself or on a derivative thereof
- Loss of drying (makes mp more useful)
List of test for inclusion in metronidazole specification- Impurities
- Related substances
- Processing plant related
- Solvents
- Water
List of test for inclusion in metronidazole specification- Assay
- A precise method to determine the absolute drug content
Metronidazole Benzoate synthesis
What types of information about the pharmaceutical product can be determined by spectroscopy- UV
- Electron conjugation
- Single, double or triple bonds
- Functional groups
- Acid or base
- Purity
What types of information about the pharmaceutical product can be determined by spectroscopy- IR
- Functional groups: distinguish between
- Carboxylic acids
- Keytones
- Amines
- Amides
- Aromatics
- Aliphatics
What types of information about the pharmaceutical product can be determined by spectroscopy- NMR + MS
- Structure determination from scratch
- Comparison with an authentic reference sample
Spectroscopy involves absorption and or emission of photons
- A molecule can absorb energy and undergo a transition from a lower energy state to a higher energy state
- A molecule can only absorb at a particular frequency if there exists within the molecule a transition of magnitude
DeltaE = hv
What changes does the absorption of a light cause in a molecule
Ultraviolet- Visible spectroscopy (UV- VIS)
- All organic compounds absorb UV light, sometimes at a very short wavelength
- UV energy is similar to the bonding energy in organic molecules
- The energy absorbed promotes bonding or non-bonding electrons to higher energy, empty molecular orbitals
Ultraviolet- Visible spectroscopy (UV- VIS)
- The position of land max indicates the extent of electron distribution and extent of conjugation in drug molecules
- Only a limited amount of information about the structure of drug molecules is obtainable by UV alone
- Changes which occur upon addition of acid or base can reveal whether acidic or basic groups are present as part of an absorbing part (chromophore) of a molecule
- INCREASE in electron conjugation results in a shift of lamda max to a longer wavelength
- DECREASE in electron conjugation results in a shift of lamda max to a shorter wavelength
Quantitive analysis
-
Beer’s law
- Light absorption proportional to the concentration of absorbing species
-
Lambert’s Law
- Light absorption proportional to the path length
The Beer-Lambert law REWORKED
