vvvv Flashcards
What is the difference between precision and accuracy?
Precision refers to the repeatability of results, while accuracy refers to how close results are to the true value.
What does a precise and accurate method result in?
Results that are close to each other and also close to the true value.
What characterizes an imprecise and inaccurate method?
Results that are scattered and far from the true mean.
What is a common measure of the precision of an analysis?
Relative standard deviation (RSD).
Fill in the blank: The analysis should be ______, reliable, and truly representative of the result.
[valid]
What are some sources of error in quantitative analysis?
- Incorrect weighting
- Inefficient extraction of analyte
- Incorrect use of pipettes or volumetric flasks
- Failure to remove interference by excipients
What is a gross error?
A serious error that is easily recognized, leading to unreliable results.
What are systematic errors?
Errors that cause all results to be in error in the same direction (constant error).
What is a random error?
An error that causes results to vary around the true value without a consistent pattern.
True or False: Systematic errors can usually be eliminated.
True.
What is the significance of understanding the sources of error in analysis?
It helps in identifying when errors can be eliminated or minimized.
What is the role of validation in analytical methods?
To ensure that the method produces reliable and accurate results.
Fill in the blank: The difference between the observed result and the true answer is known as ______.
[error]
What factors contribute to imprecise and inaccurate results?
- Poorly controlled analysis
- Faults in analytical procedures
- Equipment errors
What is the consequence of using contaminated reagents?
It can lead to gross errors in the results.
What does the term ‘hygroscopic material’ refer to?
Material that absorbs moisture from the environment.
What is the impact of incomplete powdering of a sample?
It can lead to poor recovery of the analyte.
What can result from improper extraction techniques?
It can lead to inaccurate assay results.
What is the effect of using an uncalibrated burette?
It can lead to improper readings and poor measurements.
What is a repeatability in the context of precision?
The degree to which repeated measurements under unchanged conditions show the same results.
Fill in the blank: A quantitative analysis must be ______ and reliable.
[accurate]
What is the importance of having an understanding of experimental error?
It aids in proper interpretation of results.
What does it mean if assay results are reported with a range?
It indicates the variability and reliability of the measurements.
What is the significance of a true mean in results?
It indicates the expected value that results should cluster around.
What are the common types of errors in experiments?
- Gross errors
- Systematic errors
- Random errors
What is the consequence of having results that are consistently too high or too low?
It indicates a systematic error in the measurement process.
How can random errors be characterized?
They are unpredictable and can vary from one measurement to another.
What is the definition of accuracy in analytical methods?
The accuracy of an analytical procedure expresses the closeness of agreement between the accepted true value and the value found.
Accuracy is determined through the comparison of fortified and unfortified samples.
What does precision refer to in analytical methods?
The precision of an analytical procedure expresses the closeness of agreement between a series of measurements from multiple sampling of the same homogeneous sample under prescribed conditions.
Precision can be evaluated at three levels: repeatability, intermediate precision, and reproducibility.
What is repeatability in the context of precision?
Repeatability expresses the precision under the same operating conditions over a short interval of time.
What is intermediate precision?
Intermediate precision expresses variations within laboratories: different days, different analysts, different equipment.
Define reproducibility in analytical methods.
Reproducibility expresses the precision between laboratories.
What does specificity mean in analytical methods?
Specificity is the ability of an analytical procedure to measure the analyte in the presence of components which may be expected to be present.
What is the detection limit?
The detection limit is the lowest amount of analyte in a sample that can be detected but not necessarily quantified.
Define quantitation limit.
The quantitation limit is the lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy.
What is linearity in analytical methods?
Linearity is the ability to obtain test results that are directly proportional to the concentration of the analyte in the sample.
What does the range of an analytical procedure refer to?
The range is the interval between the upper and lower concentration of the analyte in the sample for which the procedure has shown suitable precision, accuracy, and linearity.
What is robustness in analytical methods?
Robustness is the measure of an analytical procedure’s capacity to remain unaffected by small, deliberate variations in method parameters.
What is ruggedness in the context of analytical methods?
Ruggedness is a measure of the reproducibility of test results under normal, expected variations in conditions such as different analysts or reagents.
Fill in the blank: The precision of an analytical procedure expresses the closeness of agreement between a series of measurements from multiple sampling of the same _______.
[homogeneous sample]
True or False: The accuracy of an analytical procedure is defined as the closeness of agreement between different laboratories.
False
What are the three levels of precision?
- Repeatability
- Intermediate precision
- Reproducibility
What is the significance of method validation?
Method validation ensures reliability and accuracy of analytical procedures.
What should be established to ensure stability in analytical methods?
Stability should be established by keeping the sample at or below the required conditions and injecting it at regular intervals without significant variations.
Fill in the blank: The _______ of an analytical procedure is the measure of its capacity to remain unaffected by small, deliberate variations in method parameters.
[robustness]
What is the minimum specified range for the assay of an active pharmaceutical ingredient?
Normally from 80% to 120% of the test concentration.
What is the acceptable range for content uniformity testing?
Covering a minimum of 70% to 130% of the test concentration.
What does ruggedness refer to in analytical methods?
The degree of reproducibility of test results of the analysis of the same samples under various normal test conditions such as different labs, analysts, and reagent lots.
Ruggedness indicates reliability under normal operational conditions.
How is sensitivity defined in the context of analytical methods?
Sensitivity is equal to the slope of the calibration line in a linear relationship.
A higher slope indicates greater sensitivity.
What is the mean in statistics?
The sum of individual results divided by the number of measurements (n).
For an infinite population, the mean is represented by the symbol μ.
Define median.
The middle value in a set of results.
For an even number of samples, it is the average of the two middle values.
What is range in statistics?
The difference between the highest and lowest values in a set of results.
What is absolute error (AE)?
The difference between the measured value and the true value (AE = X - T).
Define relative error (RE).
The expression of the absolute error relative to the size of the measured quantity, expressed as a percentage or parts per thousand (RE = (X - T) / T x 100).
What is individual deviation from the average (d)?
The deviation or difference between each individual result and the average value (d = x - X).
What is standard deviation (SD)?
The square root of the variance, representing the spread of values around the mean.
What is variance in statistics?
The square of the standard deviation (Variance = SD^2).
Define relative standard deviation (RSD).
The standard deviation expressed as a percentage of the mean (RSD = (SD / mean) x 100).
What is the standard error of the mean (sx)?
The standard deviation divided by the square root of the sample size (sx = SD / √n).
What is the Q-test used for?
To evaluate whether a value is an outlier by comparing its deviation from the nearest neighbor.
If the calculated Q value exceeds the tabulated value, the result can be discarded with 90% confidence.
What is a confidence interval?
A range of values derived from sample statistics that is likely to contain the true population parameter.
What does regression analysis examine?
The relationship between variables, typically expressed in the form Y = a + bX, where b is the slope and a is the intercept.
What is the definition of drug stability?
The capability of a product to retain its efficacy, properties, and characteristics within specific limits throughout its shelf life.
What is the recommended shelf life for commercial pharmaceutical products?
3-5 years, during which potency should not fall below 90-95%.
No change in physical properties should occur during this time.
List the types of stability studies relevant to pharmaceutical products.
- Chemical and photochemical stability
- Physical stability
- Microbiological stability
- Therapeutic stability
- Toxicological stability
What factors affect the chemical stability of drugs?
- Storage conditions (temperature, light, humidity, oxidation)
- Selection of proper containers (plastic or glass)
- Anticipation of interactions between drug and excipients
What is the purpose of stability studies in pharmaceuticals?
To ensure that drugs maintain their intended efficacy, safety, and quality throughout their shelf life.
What is the importance of chemical stability of a drug?
It is important for:
* Storage conditions against temperature, humidity, and oxidation
* Selection of proper containers (plastic or glass)
* Anticipation of interactions between drug and excipients
Chemical stability ensures that the drug maintains its efficacy and safety during its shelf life.
What are the common chemical reactions that cause drug degradation?
Chemical degradation includes:
* Hydrolysis
* Oxidation
* Isomerization
* Racemization
* Transesterification
* Photochemical reactions
These processes can lead to reduced potency or safety of the drug.
What is hydrolysis in the context of drug degradation?
It is the most common pathway in drug instability, involving the reaction of a drug with water or acids/bases, leading to drug cleavage.
Hydrolysis often affects drugs with hydrolysable functional groups.
What is ester hydrolysis?
Hydrolysis of a drug with an ester functional group, which is a common type of drug instability. Examples include procaine, aspirin, and atropine.
Ester hydrolysis is particularly significant in pharmaceutical formulations.
What is amide hydrolysis?
Amides are generally more stable to hydrolysis, which can occur through general acid and base catalysis.
Examples include penicillins and cephalosporins that decompose in the presence of hydrogen ions.
What are the three regions of pH profile in drug hydrolysis?
The three regions are:
* Catalyzed region (H+) with slope -1
* Uncatalyzed region with slope 0
* Hydroxyl ion catalyzed region (OH-) with slope +1
The pH can significantly affect the rate of hydrolysis.
What is oxidation in drug degradation?
It is the removal of electrons from a molecule, loss of hydrogen (dehydrogenation), or addition of oxygen. Autoxidation is a common pathway involving molecular oxygen.
Oxidation can lead to the conversion of alcohols to ketones or aldehydes.
List other degradation reactions besides hydrolysis and oxidation.
Other degradation reactions include:
* Addition
* Elimination
* Isomerization
* Epimerization
* Polymerization
* Acylation
* Transesterification
* Radiation-induced reactions
* Photolysis
These reactions can further complicate drug stability.
What factors enhance the reaction rate of drug degradation?
Factors include:
* Temperature
* pH
* Solvent
* Drug concentration
* Interaction between components
* Ionic strength
* Trace metal catalysis
Understanding these factors helps in formulating stable drugs.
What is the Arrhenius equation used for?
It relates the reaction rate constant (k) to temperature (T) and activation energy (Ea).
The equation is given as: k = Ae^(-Ea/RT), where R is the gas constant.
What is the effect of pH on drug degradation?
Many drugs depend on their functional groups to give specific acidic or basic catalysis. The stability is often highest in a pH range of 4-8.
pH can influence the rate of hydrolysis and other degradation reactions.
Describe the effect of drug concentration on degradation.
The effect depends on the order of the reaction:
* Zero Order: reaction rate is linear with time, independent of concentration
* First Order: reaction rate depends on the concentration of one species
* Second Order: reaction rate depends on the concentration of two species
Different orders of reaction define how the concentration affects the rate of degradation.
What is the significance of trace metal catalysis in drug formulations?
Trace metals can catalyze auto-oxidation reactions, complicating the preparation of stable solutions for oxidizable drugs.
Example: Formation of colored ephedrine solution increases in the presence of metals like Fe++, Cu++, and Co++.
What is the definition of shelf-life in pharmaceuticals?
Shelf-life is the time period during which a product retains its specified characteristics and can be used safely.
Shelf-life can be influenced by stability, storage conditions, and formulation.
What are the five types of stability important to pharmacists?
The five types are:
* Chemical Stability
* Physical Stability
* Microbiological Stability
* Therapeutic Stability
* Toxicological Stability
Each type of stability ensures the drug remains effective and safe for use.
Fill in the blank: The loss of drugs in zero-order reactions is _______.
independent of the concentration of reactants.
Fill in the blank: The half-life for first-order reactions is given by _______.
T1/2 = 0.693/k.
True or False: Most drugs are most stable between pH range 4-8.
True
What is chemical stability important for?
Selecting storage conditions (temperature, light, humidity) and anticipating interactions when mixing drugs and dosage forms.
What are stability and expiration dating based on?
Reaction kinetics, which is the study of the rate of chemical change influenced by conditions such as concentration, products, and other chemical species.
What does reaction order indicate?
The overall order (sum of exponents of concentration terms) or the order with respect to each reactant.
What are the two most common reaction orders encountered in pharmacy?
Zero-order and first-order reactions.
Define zero-order kinetics.
The loss of drug is independent of the concentration of reactants and constant with respect to time.
What is the mathematical expression for zero-order kinetics?
C = -kt + C0, where C is the concentration at time t, k is the zero-order rate constant, and C0 is the initial concentration.
In a zero-order reaction, if a drug suspension decays with a reaction rate constant of 0.5 mg/mL/hr, what is the concentration after 72 hours from an initial concentration of 125 mg/mL?
89 mg/mL.
How long will it take for a drug suspension to reach 90% of its original concentration?
25 hours.
What is the Arrhenius equation used for?
To calculate the rate constant and activation energy for chemical reactions.
What is the slope of the plot of log K vs. 1/T in the Arrhenius equation?
-Ea/2.303R.
What factors can lead to the formation of impurities in pharmaceutical chemicals?
- Raw material used
- Method of manufacture
- Stability of product
- Physical contamination sources
- Storage conditions.
What are the two main sources of raw materials in pharmaceuticals?
- Biological sources
- Chemical starting materials.
What type of contamination can arise from the manufacturing process?
- Starting material and its impurities
- Intermediates
- Reagents, solvents, and catalysts used in the process.
What is a key method to prevent hydrolysis in pharmaceutical compounds?
Strict control of pH and avoiding contact with metal surfaces during storage.
What are light-sensitive materials required to do?
Store under dark conditions.
What can changes in particle size and form lead to?
Marked changes in therapeutic efficiency of the product.
What types of contamination are associated with manufacturing?
- Particulate contamination
- Non-particulate contamination
- Cross-contamination.
True or False: Chemical changes can occur in stored products due to temperature changes.
True.
Fill in the blank: The nature of decomposition can be predicted from knowledge of the _______.
properties of the substance.
What is non-particulate contamination?
Gaseous atmospheric pollutants
Refers to contamination that does not involve solid particles but rather gases in the atmosphere.
What is cross-contamination?
Handling errors during the production of injectables, tablets, and other pharmaceuticals
This can occur when different products or ingredients unintentionally mix.
What are sterility tests used for?
To ensure the sterility of all products intended for parenteral administration, ophthalmic preparation, etc.
These tests must be conducted under aseptic conditions.
What is the difference between process errors and packing errors?
Process errors arise from incomplete solution of solute; packing errors involve products with similar appearance leading to potential mislabeling.
Process errors can be detected through normal analytical control procedures.
What are organic impurities?
Impurities that can arise from contamination, malicious adulteration, or contamination of active ingredients or finished products
These impurities present more complex analytical challenges.
What are mineral impurities?
Heavy metals and certain other inorganic impurities
These are determined by flame photometric emission spectrometry or atomic absorption spectrophotometry.
What factors influence the acceptable limit for impurities in drugs?
- Toxicity of the impurity
- Dose and duration of treatment
- Route of administration
Unknown impurities should be less than 0.1% and detectable.
What types of specifications control pharmaceutical products?
- Manufacturing product license standards
- Pharmacopoeia standards
These specifications help maintain the quality and safety of pharmaceutical products.
What is the role of a pharmaceutical analyst in quality control?
Responsible for testing random samples of raw materials, ensuring compliance with specifications, and participating in inspections
They play a key role in maintaining good manufacturing practices (GMP).
What challenges do counterfeit drugs pose?
- Difficult to trace
- Spreading can’t be controlled
- Can deceive non-experts
Counterfeit drugs often look similar to genuine products, making them hard to identify.
What are counterfeit drugs defined as?
Medicines that are deliberately and fraudulently mislabeled with respect to identity and/or source
This includes both generic and branded products.
What is the purpose of batch quality assurance?
To ensure that a single batch of material or product is homogenous and meets quality standards
It involves tracking batch numbers for identification and compliance.
Fill in the blank: The pharmaceutical analyst is responsible for testing drug _______.
samples
This includes checking for conformity with standards and specifications.
True or False: All impurities in pharmaceutical products must be completely eliminated.
False
Some impurities are allowed within acceptable limits depending on their toxicity and the drug’s intended use.
What do acceptable dosage forms ensure?
Safety and efficacy of the pharmaceutical product
Dosage forms must be appropriately packed and labeled.
What are the responsibilities of a pharmaceutical analyst?
- Testing raw materials
- Evaluating batch certificates
- Participating in drug inspections
- Ensuring compliance with GMP
Their work is critical for maintaining drug quality and safety.
What is packaging?
Packaging is defined as the collection of different components which surround the pharmaceutical product from the time of production until its use.
What are the key protective roles of packaging?
- Protect against adverse external influences that can alter the properties of the product
- Protect against biological contamination
- Protect against physical damage
- Carry correct information and identification of the product
- Provide tamper evidence and child resistance
- Help prevent counterfeiting
What are the additional qualities required of packaging materials?
- Must preserve the physical properties of all forms
- Must not alter the product
- Must comply with specifications
- Must protect against undesirable or adulterating entities
What is the purpose of separation of mixtures in pharmaceuticals?
To isolate specific compounds from a mixture for analysis or formulation purposes.
Fill in the blank: The structures and pKa values of aspirin, paracetamol, and codeine are as follows: Aspirin pKa = ______, Paracetamol pKa = ______, Codeine pKa = ______.
Aspirin pKa = 2.5, Paracetamol pKa = 9.5, Codeine pKa = 8.2
True or False: All three drugs (aspirin, paracetamol, codeine) are soluble in toluene in their unionised form.
True
What is the sequence of ionisation for the separation of codeine?
Addition of dilute hydrochloric acid will ionise codeine and form codeine hydrochloride, which is water soluble.
What is the role of a strong base in the separation of aspirin and paracetamol?
A strong base (e.g., sodium hydroxide) will ionise both acids to facilitate their separation.
What happens to codeine during the separation process?
Codeine is ionised to codeine hydrochloride, which partitions into the aqueous phase.
How is pure codeine obtained after separation?
By removing the aqueous phase and adding a strong base to liberate codeine base in the organic phase.
What is the effect of pH on the solubility of drugs during separation?
pH affects the ionisation of drugs, influencing their solubility in either aqueous or organic phases.
Fill in the blank: The separation of aspirin, paracetamol, and codeine can be achieved using ______ and a separating funnel.
immiscible solvents
What is the outcome of adding hydrochloric acid during the separation of the drugs?
It ionises codeine, allowing it to be extracted into the aqueous phase.
What is the final step in obtaining aspirin after its separation?
Evaporation of the volatile solvent yields pure aspirin.
What is the significance of drug pKa values in pharmaceutical analysis?
pKa values determine the ionisation state of drugs and their solubility in different solvents.
