Ensuring the stability and compatibility of sterile preparations is a cornerstone of safe and effective pharmacy practice, particularly in hospital and infusion settings. For PharmD students, mastering these concepts is critical to preventing therapeutic failures, adverse drug events, and patient harm. This area of study, guided by standards like USP Chapter <797>, involves understanding the complex interplay of physicochemical factors that can affect a medication from the moment it is compounded until it is administered. This includes recognizing factors that degrade drug molecules, such as hydrolysis and oxidation, and identifying potential incompatibilities between drugs and intravenous fluids or other medications. A thorough knowledge of how to determine Beyond-Use Dates (BUDs), interpret compatibility resources like Trissel’s Handbook, and visually inspect preparations is essential for any pharmacist responsible for sterile compounding. This quiz is designed to test your knowledge on these vital topics and prepare you for real-world scenarios you will encounter in your practice.
1. Which of the following is the most common chemical degradation pathway for drugs in aqueous solutions?
- A. Oxidation
- B. Photolysis
- C. Hydrolysis
- D. Isomerization
Answer: C. Hydrolysis
2. A physical incompatibility in an IV admixture is most likely to be observed as which of the following?
- A. Formation of a therapeutically inactive complex
- B. A change in the pH of the solution
- C. The formation of a precipitate
- D. A loss of drug potency over time
Answer: C. The formation of a precipitate
3. According to USP Chapter <797>, the Beyond-Use Date (BUD) for a medium-risk level compounded sterile product (CSP) stored at room temperature is generally:
- A. 12 hours
- B. 24 hours
- C. 30 hours
- D. 48 hours
Answer: C. 30 hours
4. The ‘salting out’ phenomenon, where a precipitate forms due to high salt concentration, is an example of what type of incompatibility?
- A. Chemical
- B. Physical
- C. Therapeutic
- D. pH-related
Answer: B. Physical
5. Which factor is LEAST likely to affect the stability of a parenteral medication?
- A. Temperature
- B. Light exposure
- C. Route of administration
- D. pH of the solution
Answer: C. Route of administration
6. A pharmacist is preparing an admixture of calcium gluconate and potassium phosphate. What potential incompatibility should the pharmacist be most concerned about?
- A. Gas evolution
- B. Color change
- C. Precipitation of calcium phosphate
- D. Hydrolysis of calcium gluconate
Answer: C. Precipitation of calcium phosphate
7. Which of the following is considered the most comprehensive and widely used reference for information on the compatibility and stability of injectable drugs?
- A. The United States Pharmacopeia (USP)
- B. The Handbook of Nonprescription Drugs
- C. King Guide to Parenteral Admixtures
- D. Trissel’s Handbook on Injectable Drugs
Answer: D. Trissel’s Handbook on Injectable Drugs
8. Oxidation of a drug can often be minimized by adding which of the following to the formulation?
- A. A chelating agent like EDTA
- B. A buffering agent
- C. An antioxidant like ascorbic acid
- D. A surfactant
Answer: C. An antioxidant like ascorbic acid
9. What is the term for the instability of a Total Parenteral Nutrition (TPN) admixture that results in the separation of the lipid phase into a visible layer of oil on the surface?
- A. Cracking
- B. Creaming
- C. Coalescence
- D. Aggregation
Answer: A. Cracking
10. A drug solution is most stable at a pH of 4.5. If it is added to an IV fluid with a pH of 7.0, what is the likely outcome?
- A. The drug will become more soluble.
- B. The rate of degradation will likely increase.
- C. The solution will become supersaturated.
- D. The drug’s therapeutic effect will be enhanced.
Answer: B. The rate of degradation will likely increase.
11. What does the term “leaching” refer to in the context of IV containers?
- A. The movement of drug into the plastic of the IV bag.
- B. The movement of chemical components from the plastic container into the solution.
- C. The degradation of the drug due to light exposure through the container.
- D. The evaporation of the solvent through the container walls.
Answer: B. The movement of chemical components from the plastic container into the solution.
12. When compounding a multi-drug IV admixture, which principle regarding the order of mixing is generally recommended to prevent precipitation?
- A. Add the most concentrated drug last.
- B. Mix the electrolytes first.
- C. Dilute each drug as much as possible before mixing.
- D. Add potassium phosphate and calcium salts consecutively.
Answer: C. Dilute each drug as much as possible before mixing.
13. A high-risk level compounded sterile product (CSP) that is prepared without passing a sterility test has a BUD of ____ when stored at refrigerated temperatures.
- A. 24 hours
- B. 48 hours
- C. 72 hours
- D. 7 days
Answer: C. 72 hours
14. Photodegradation of a drug can be prevented by:
- A. Refrigerating the product.
- B. Using an in-line filter during administration.
- C. Dispensing the drug in an amber-colored or opaque container.
- D. Adjusting the pH of the solution.
Answer: C. Dispensing the drug in an amber-colored or opaque container.
15. Sorption is a physical incompatibility that involves:
- A. The release of gas from a solution.
- B. The loss of drug from solution due to binding to the surface of a container or tubing.
- C. The formation of a solid precipitate.
- D. The separation of oil and water phases.
Answer: B. The loss of drug from solution due to binding to the surface of a container or tubing.
16. Which of the following drugs is well-known to have significant sorption issues with PVC containers?
- A. Penicillin G
- B. Insulin
- C. Heparin
- D. Amiodarone
Answer: D. Amiodarone
17. What is the primary purpose of a Beyond-Use Date (BUD)?
- A. To indicate when the drug should be administered to the patient.
- B. To provide the date after which a CSP should not be used.
- C. To indicate the manufacturer’s expiration date.
- D. To track the inventory of the drug.
Answer: B. To provide the date after which a CSP should not be used.
18. The stability of a drug is defined as the extent to which it retains, within specified limits, and throughout its period of storage and use:
- A. Only its chemical properties.
- B. Only its physical properties.
- C. The same properties and characteristics that it possessed at the time of its manufacture.
- D. Its original color and clarity.
Answer: C. The same properties and characteristics that it possessed at the time of its manufacture.
19. A ‘Y-site’ refers to:
- A. The part of the IV tubing where the spike enters the bag.
- B. An injection port on the side of the main IV line used for administering a second medication.
- C. The roller clamp used to control the flow rate.
- D. The drip chamber of an IV set.
Answer: B. An injection port on the side of the main IV line used for administering a second medication.
20. What is a key consideration for the stability of biologic medications like monoclonal antibodies?
- A. They are highly resistant to temperature changes.
- B. They are prone to denaturation and aggregation if shaken or agitated.
- C. They are most stable in highly acidic solutions.
- D. They are not affected by freezing.
Answer: B. They are prone to denaturation and aggregation if shaken or agitated.
21. A color change in an IV solution, such as dopamine turning pink, is an indication of what process?
- A. Precipitation
- B. Oxidation
- C. Hydrolysis
- D. Leaching
Answer: B. Oxidation
22. Which information is generally NOT found in a standard Trissel’s monograph?
- A. Solution compatibility
- B. Y-site compatibility
- C. Therapeutic indications
- D. Stability with freezing
Answer: C. Therapeutic indications
23. Compounding a TPN is considered what risk level according to USP <797>, assuming it involves combining more than three sterile commercial products?
- A. Low-risk
- B. Medium-risk
- C. High-risk
- D. Immediate-use
Answer: B. Medium-risk
24. The BUD of a compounded sterile product can be extended beyond the USP <797> defaults if:
- A. The pharmacist has extensive experience.
- B. The product is for a pediatric patient.
- C. There is published stability data from a peer-reviewed journal supporting a longer BUD.
- D. The product is stored in a glass container.
Answer: C. There is published stability data from a peer-reviewed journal supporting a longer BUD.
25. A pharmacist notices that a TPN solution appears milky or has a creamy layer. This is known as creaming and is a sign of:
- A. The initial stage of lipid emulsion instability.
- B. A normal variation in appearance.
- C. Calcium-phosphate precipitation.
- D. Bacterial contamination.
Answer: A. The initial stage of lipid emulsion instability.
26. What is the primary reason for using a 0.22-micron filter for sterilizing a solution?
- A. To remove particulate matter.
- B. To remove endotoxins.
- C. To remove bacteria.
- D. To remove viruses.
Answer: C. To remove bacteria.
27. What type of incompatibility occurs when two or more drugs are administered together, resulting in an undesirable alteration of the therapeutic effect of one or more of the drugs?
- A. Physical
- B. Chemical
- C. Therapeutic
- D. Allosteric
Answer: C. Therapeutic
28. Why is it generally recommended to add the multivitamin infusion (MVI) to the TPN admixture last?
- A. It is the most concentrated ingredient.
- B. It is highly acidic and can affect other components.
- C. It is sensitive to light and its addition initiates the need for light protection.
- D. It can act as a catalyst for oxidative degradation of other components.
Answer: C. It is sensitive to light and its addition initiates the need for light protection.
29. The term “shelf life” refers to:
- A. The time a CSP can be used after it has been opened.
- B. The time from the date of manufacture during which a drug product is expected to remain within its approved specifications.
- C. The BUD assigned by the compounding pharmacy.
- D. The time it takes for 50% of the drug to degrade.
Answer: B. The time from the date of manufacture during which a drug product is expected to remain within its approved specifications.
30. Which of the following would be classified as a high-risk compounding activity?
- A. Reconstituting a single vial of antibiotic for one patient.
- B. Preparing a TPN for one patient using an automated compounding device.
- C. Using non-sterile bulk powder to prepare a sterile solution.
- D. Transferring a solution from one sterile container to another.
Answer: C. Using non-sterile bulk powder to prepare a sterile solution.
31. The pH of a solution can significantly impact drug stability, primarily by affecting the rate of:
- A. Hydrolysis and oxidation.
- B. Leaching and sorption.
- C. Denaturation.
- D. Precipitation.
Answer: A. Hydrolysis and oxidation.
32. What is the purpose of a chelating agent, such as edetate disodium (EDTA), in a parenteral formulation?
- A. To act as a buffer.
- B. To bind with trace heavy metal ions that can catalyze oxidative degradation.
- C. To serve as a preservative.
- D. To increase the solubility of the drug.
Answer: B. To bind with trace heavy metal ions that can catalyze oxidative degradation.
33. An ampule is a:
- A. Multi-dose vial with a rubber stopper.
- B. Sealed glass container with a single dose of medication that must be broken to access the drug.
- C. Plastic IV bag.
- D. Pre-filled syringe.
Answer: B. Sealed glass container with a single dose of medication that must be broken to access the drug.
34. What is a major stability concern with drugs formulated in plastic IV containers made of DEHP-plasticized PVC?
- A. Leaching of DEHP into the IV fluid.
- B. The container is permeable to oxygen.
- C. The container is opaque to light.
- D. The plastic is very brittle.
Answer: A. Leaching of DEHP into the IV fluid.
35. A BUD for a low-risk CSP stored in the freezer is typically:
- A. 14 days
- B. 30 days
- C. 45 days
- D. 60 days
Answer: C. 45 days
36. A hazy or cloudy appearance in an IV solution that should be clear is a potential sign of:
- A. Gas evolution.
- B. Drug adsorption.
- C. A physical incompatibility or microbial growth.
- D. A simple dilution effect.
Answer: C. A physical incompatibility or microbial growth.
37. Which of the following factors generally increases the rate of chemical reactions and thus decreases drug stability?
- A. Lowering the temperature.
- B. Increasing the temperature.
- C. Using a light-protective cover.
- D. Storing the product in a glass vial.
Answer: B. Increasing the temperature.
38. What is the “cracking” of a TPN emulsion considered?
- A. A reversible sign of instability.
- B. A safe, though undesirable, outcome.
- C. An irreversible sign of instability, making the TPN unsafe for use.
- D. A sign that the TPN needs to be shaken well.
Answer: C. An irreversible sign of instability, making the TPN unsafe for use.
39. When evaluating compatibility information, what does ‘Y-site compatibility’ refer to?
- A. The compatibility of two drugs mixed in the same syringe.
- B. The compatibility of two drugs infused sequentially through the same line.
- C. The compatibility of two drugs administered simultaneously at a Y-injection port.
- D. The compatibility of a drug with the IV container material.
Answer: C. The compatibility of two drugs administered simultaneously at a Y-injection port.
40. A drug is supplied as a lyophilized (freeze-dried) powder. This is done to:
- A. Make the drug easier to see.
- B. Increase the stability of drugs that are unstable in aqueous solution.
- C. Ensure the drug is already sterile.
- D. Decrease the cost of manufacturing.
Answer: B. Increase the stability of drugs that are unstable in aqueous solution.
41. The BUD for an immediate-use CSP is:
- A. 1 hour from the start of compounding.
- B. 4 hours from the start of compounding.
- C. 12 hours from the start of compounding.
- D. 24 hours from the start of compounding.
Answer: A. 1 hour from the start of compounding.
42. Which of the following is a key component of ensuring TPN stability related to electrolytes?
- A. Always add calcium and phosphate salts together.
- B. Check the calcium-phosphate solubility curve.
- C. Add lipids last.
- D. Administer the TPN at a slow rate.
Answer: B. Check the calcium-phosphate solubility curve.
43. The presence of gas bubbles evolving from an admixture is a sign of what type of incompatibility?
- A. Physical
- B. Chemical
- C. Sorption
- D. Therapeutic
Answer: B. Chemical
44. What is the primary stability concern for phenytoin when it is diluted?
- A. It is highly susceptible to photolysis.
- B. It is only stable in a very narrow pH range and can precipitate easily.
- C. It readily oxidizes upon exposure to air.
- D. It adsorbs to glass containers.
Answer: B. It is only stable in a very narrow pH range and can precipitate easily.
45. When a pharmacist is unsure about the compatibility of two drugs in an IV admixture and cannot find data in reliable resources, the most appropriate action is to:
- A. Mix them and observe for any changes.
- B. Assume they are compatible if they are in the same therapeutic class.
- C. Compound them together but label with a short BUD.
- D. Contact the drug manufacturers or dispense and administer them separately.
Answer: D. Contact the drug manufacturers or dispense and administer them separately.
46. Which of the following is NOT a primary factor influencing a drug’s stability?
- A. The drug’s inherent chemical structure
- B. The patient’s age
- C. Storage temperature
- D. The presence of catalysts
Answer: B. The patient’s age
47. A “Single-Dose Vial” (SDV) after being punctured in an ISO 5 environment may be used for up to:
- A. 1 hour
- B. 6 hours
- C. 12 hours
- D. 24 hours
Answer: C. 12 hours
48. Why are parenteral solutions ideally isotonic?
- A. To ensure they are sterile.
- B. To maximize drug solubility.
- C. To minimize pain and tissue damage at the injection site.
- D. To improve drug stability.
Answer: C. To minimize pain and tissue damage at the injection site.
49. What is the primary purpose of visual inspection of a CSP before it is dispensed?
- A. To confirm the correct drug was used.
- B. To check for particulate matter, precipitation, color change, or other signs of instability/incompatibility.
- C. To verify the correct volume was added.
- D. To ensure the label is correct.
Answer: B. To check for particulate matter, precipitation, color change, or other signs of instability/incompatibility.
50. What does the term “adsorption” refer to in the context of drug stability?
- A. The chemical degradation of a drug.
- B. The uptake of water by a formulation.
- C. The binding of drug molecules to the surface of a container.
- D. The formation of a less soluble crystalline form.
Answer: C. The binding of drug molecules to the surface of a container.