Genetic Factors QA/QC Flashcards
what are 4 fundamental principles when using a plant as a medicine that if not met could have a deleterious effect
- that you have the right plant
- the plant contains the correct chemical constituents
- the constituents are at the right levels or quantities
- there is consistency from batch to batch
what is the primary reason that plant based drugs fail to meet the 4 fundamental requirements
- they are biological in nature, derived from secondary metabolism
- the natural inherent variability in this process may impact level of secondary metabolite available and yields
what are the three most important EU guidelines on medicinal plants
- annex 7 of GMPs
- Good Agricultural Collection Practices
- Quality of herbal medicinal products
what are the contents of a monograph (4) and what is commonly included in each section
- definition
- Latin Botanical name, common name, minimum content
- identification
- micro and macroscopic, may include drawings of cell inclusions
- TLC
- Purity Test - by TLC may include absence of certain bands/impurities
- Tests
- loss on drying, total ash, acid insoluble ash
- assay
- HPLC, GC, colorimetric or titrimetric
if there is no monograph what is expected
that you develop an inhouse monograph
in addition to the contents of a standard monograph, what does an in house monograph also require (4)
- information on the site collection, time of harvest, stage of crop at harvest, treatments during growth, drying and storage conditions
- microbial quality tests (bacteria and fungi)
- residues - pesticides, fumigants, heavy metals
- a quantitative assay for the content of the phytochemical
what are 4 factors that impact the quality of a plant based medicinal product
- genetic
- environmental or ecological
- post harvest handling
- method of storage
genetic factors relate to the inherent variability of organsisms and can improve quality by altering genetic structure through (2)
natural selection or genetic manipulation
most plants are haploid or diploid
diploid (2n)
polyploid organisms have how many chromosomes
3 or 4n
autoploid
multiplication of chomosomes from a single species e.g. valerian
alloploid
hybridization of 2 species (peppermint)
what is hybridization
genetic manipulation by crossing 2 plants
how are polyploids created
- often induced by heating seeds with colchicine or ionizing radiation
- formed as allo or autoploids
what are chemical races
- a form of genetic variation - chemotype or chemodemes
- similar physical characteristics but different chemical characterisitics e.g. cannabis (THC and CBD)
what is a chemovar
a different form of a medicine
how do environmental factors influence the quality of medicines by impacting (4 things)
- phytomass (biomass),
- amount of dry matter produced,
- ratio of plant organs, and
- level of active subsituent
what are the 2 environmental factors which influence quality of medicines
- climate
- soil
what are 3 factors of climate that influence quality of medicines
light and temperature and moisture
how do the climatic factors of light, temperature and mositure influence the quality of medicines
- light
- required for growth of plant and primary metabolism (photosynthesis)
- affects amount of phytomass and level of active compounds
- temperature
- higher temps generally increase metabolism and therefore increase amount of active constituent
- moisture
- rain, dew, humidity, irrigation
- needed for growth, however if too much, can cause fungal growth/disease
what is an example of how temperature impacts constituents of plants
Linseed oil
- northern climate - more unstaturated fatty acids
- southern climate - low unstaturated fatty acid levels
what are the implications to quality control of climate on medicinal products? (1)
how can these be managed? (1)
- hard to control and therefore get year to year and site to site variation
- by monitoring the variation through chemical assays and throughout the growth lifecycle
what are the chemical assays that can be used to assess the implication of climate on medicinal products (4)
- colourimetric
- titrimetric
- spectrophotmetric
- chromatographic
what are the 4 targets for assays which assess variability of medicines as a result of climatic factors of light, temperature and moisture
- known active constituents
- active constituent markers
- analytical markers characteristic of the species but those which may not contribute to therapeutic effect
- ubiquitous markers
how does the environmental factor of soil influence medicinal products (3)
- fundamental basis of crop production
- provides nutrients, air and water
- also is a source of pests, toxic substances or fungi that can affect the crop
what is the most important factor of soil that influences the yield of secondary metabolites and why
soil chemistry, it is the basis of growth and is amenable to alteration
what are the 2 subdivisions of chemicals related to soil chemistry that are required for plant growth
- macro nutrients
- N, K, PO3 and lime
- applied as natural or artificial fertilizers
- micro nutrients
- boron, zinc, copper, cobalt, iron, magnesium
- required in trace amounts
what can a deficiency in micro nutrients result in
disturbance in growth, leading to loss of active chemical
what is the impact of the environmental factor of soil on QC processes
what measurements can be made to assess the impact of this issue? (3)
- soil is variable from site to site, and country to country, cannot be standardized
- therefore need to monitor with QC assays
- Good Agricultural Collection Practices
- record the weather extremes, and any fertilizers or pesticides used
- describe the site of collection
- consider near by crops or previous crops for risk of X-contamination
the time and method of harvest is important because (2)
- the timing can influence when the plant should be harvested e.g. when the most active constituent is present, stage of growth
- harvest method can influence enzymatic effect on the active whether desirable or undesirable
when should the constituent content be monitored during the growth period and how
- throughout the growth period to determine when the desired constituent is at its peak level
- monitored via chemical assays, chromatographic methods or radioimmunoassay or ELISA
when herbs are not cultivated but collected from nature, what is this called?
what practices need to be followed for collection?
what is of particular importance for the persons doing the collection?
- wild crafted herbs
- CITES - Convention on International Trade and Endangered Species
- training to ensure proper identification of the right plant and personal hygiene to avoid collecting contaminated plants
- those that are grown by contaminated areas (e.g. next to a dump or farmer’s cow/pig field
- contamination by the collector themselves
the purpose of monitoring the content of constituents during the growth season is to eliminate
the natural variability in the level of constituents present in a plant during to the growth season known as ontogenic variability
what is post harvest enzyme activity and why does it occur
- post enzyme harvest activity are enzyme catalyzed biochemical reactions that take place after harvest has occurred
- after harvest, the plant enzymes continue to function
- can result in desirable or undesirable changes
what are some desirable post harvest enzyme activity effects
- some compounds are only formed as a result of post harvest enzyme activity
- e.g. vanillin is formed in the vanilla pod by fermentation post harvest
- the enzyme catalyzes the hydrolysis of the glycoside
what is are 2 undesirable effect of post harvest enzyme activity
- loss of active substances, degradation
- creation or formation of toxic substances
what are 4 methods by which post eznyme activity can be prevented where enzyme effect is damaging
- heat stabilization
- freezing
- freeze drying
- rapid dehydration by drying
most damaging post harvest enzymes are _________which require_______and therefore controlling ________controls enzyme activity
- hydrolases
- moisture
- moisture levels
what level of moisture is considered dry
5-10%
this type of drying prevents decay and rotting and stops hyrolysis by
- rapid drying
- denaturing of the proteinaceous enzymes
drying can be carried out at temperatures above and below the optimum temperature for the enzyme. what are the advantages/disadvantages of each
- above optimal
- degrade the enzymes, prevent damaging effects of post harvest enzyme activity
- may degrade the active
- below optimal
- safe for temperature labile actives
- longer time to dry
what are the heat sources for drying
- direct/indirect sunlight
- drying sheds/chambers
what can happen to a drug during storage that may have an impact on the quality of the medicine (3)
- all drugs will absorb moisture upon storage
- spoilage
- changes to the drug actives or inactives may occur during storage
- adulteration during storage
what are 5 types of chemical changes that can occur during storage
- enzymatic transformation
- keep dry to prevent re-activation of enzymes
- oxidation
- oxidation of volatile oils, lose scent
- rancidification
- volatilization
- storage at high T results in loss through evaporation
- photochemical
- exposure to light can cause changes in constituent levels
what are the QC implications of storage of crude drugs,i.e. what should be monitored or implemented (5)
- need to monitor during storage
- establish stability
- protect from light, rodents, other pests
- record the drying
- do not store for long periods of time, deliver to next part of supply chain
what are 6 forms of contamination which impact vegetable drugs
- microbial
- pests (insects or rodents)
- heavy metals
- radionucleotides
- pesticides
- synthetic drugs
for each of the below sources of contamination what are methods of prevention or control
- microbial
- pests (insects or rodents)
- heavy metals
- radionucleotides
- pesticides
- synthetic drugs
- training for collection on hygiene, adequate storage
- use of dry or moist heat, fumigation, gamma irradiation, pressurized CO2, microwaves
- monitoring using AA or ICPMS
- testing depenent upon the location of acquisition e.g. if from easter europe or somewhere where there has been or is known radioactivity
- GC with electron-capture detection analyzer
- testing
what are three categories of microbial quality as defined in ph Eur
- A - medicinal products with herbals intended for infusion
- e.g. teas - use boiling water
- B - made fro extracts/herbal drugs where the method of extraction uses pre-treatment with steam to reduce microbial levels
- C - extracts of herbs where the method of extraction uses low strength alcohols or non-boiling water which does not decrease microbes to category B level
define TAMC and TYMC
which of the three categories has the most stringent criterial for TAMC and TYMC
- total aerobic microbial count; total yeast mould count
- category B
what organism is required to be absent from all 3 microbial quality levels
salmonella
what is the presence of E. coli indicative of
contamination with animal fertilizer or human excrement (used as fertilizer on land or due to poor hygiene practices in handling of drugs
why are aflatoxins a concern
they are mutagenic, carcinogenic and teratogenic
which fungus produces aflatoxins (mycotoxins)
aspergillus
what are the risk factors associated with aflatoxin development (3)
- high temperature
- high humidity
- presence of starch or lipid in materials
how are aflatoxins detected i.e. what are the QC implications of aflatoxins
- analyze via HPLC using post column derivatisation
how can insect or rodent contamination be detected
- wetting exoskeleton with parrafin & microscopic evaluation
for control methods associated with insect or pest contamination of crude drug what must be demonstrated
that the method of decontamination does not impact the constituents and that there are no harmful residues remaining
what are sources of heavy metal contamination
- environmental:
- lead from petrol, mercury, fungicidal seed dressings
- intentional
- aruveydic medicine
- arsenic is added intentionally
- chinese medicines
- mercury added intentionally
- aruveydic medicine
