Customer Service Group McGuff Compounding Pharmacy

Questions and Answers about Ascorbic Acid Injection

Q. How do I protect Ascorbic Acid from light after it is admixed in a bag?

After Ascorbic Acid has been added to an I.V. solution, the container and admixture can be protected from light by using an IV Cover, Amber, Bags/Bottles and a Light Safe IV Administration set. The admixture should be infused as soon as possible.

Q. I left my vial of Ascorbic Acid Injection out of the refrigerator at room temperature. Can I still use it?

If the vial is unused, intact, and has been out of the refrigerator for up to seven days it can be returned to refrigeration storage for future use.

It is unlikely that you will notice any product differences when an unused, intact vial is stored at room temperature for short periods of time. 

When the product is stored at room temperature for longer periods of time the solution color may change from light yellow to dark yellow/brown. You may notice this change in color when the product is withdrawn from the vial into a clear,  syringe. This is normal.  There can also be an increase in pressure build-up in the vial, this also is normal.  It is recommended to keep the vial in the refrigerator to avoid these changes. 

McGuff Compounding Pharmacy Services has performed extensive stability testing to detect changes in potency over time.  Part of the testing was performed on product stored at various room temperatures for periods up to the Beyond Use Date. The stability testing confirmed product potency remains within specification at room temperature up to the Beyond Use Date.

If this vial has been used, it should be discarded 4 hours after the initial entry regardless of the temperature during the 4 hours.

Q. Do all Ascorbic Acid Injections have the same formulation and are they made using the same process?

Only the manufacturer or the compounding pharmacy can comment on their own unique formulation and process. McGuff Compounding Pharmacy Services, Inc. applies a nitrogen overlay during the packaging process to reduce oxidation of ascorbic acid while in the vial. Please contact your supplier of Ascorbic Acid Injection; they should be able to address your concerns.

Q. Is there any way the Beyond Use Date can be extended?

An unused, intact vial of Ascorbic Acid Injection 500 mg/mL preservative free when stored according to the label instructions will remain within specification for potency and sterility until the Beyond Use Date indicated on the label. We do not have information for stability after the Beyond Use Date.

Q. Our shipment of Ascorbic Acid Injection arrived with the ice packs melted and the product was warm/hot to the touch. Can it still be used?

In general, Ascorbic Acid Injection should be refrigerated and not exposed to prolonged direct sunlight and/or elevated temperatures.

Direct sunlight: if your ascorbic acid vials were still inside the package direct sunlight should not be an issue.

Temperature During Shipment: exposure to the temperatures encountered during shipment should not adversely affect the product. McGuff Compounding Pharmacy Services has performed extensive stability testing in which the Ascorbic Acid Injection was incubated in an oven up to ~ 120 F for 7 days. The vials were then assayed for potency. The assay results demonstrated a slight loss in potency but all vials assayed remained within labeled potency.

Please examine the Ascorbic Acid Injection upon receipt. If you see signs of exterior product damage such as glass shards, cracks in vial, loose cap, etc. please call us at (877) 444-1133.

Q. What is McGuff Compounding Pharmacy Services non-corn ascorbic acid derived from?

McGuff Compounding Pharmacy Services sends a random sample of each lot of the raw material to be tested to insure it complies with USP standards. This is done to confirm the manufacture’s certificate of analysis statement indicating USP compliance.

In addition, we ensure that a random sample of each lot of raw material is analytically tested to verify the material was obtained from a non-corn source. This is done using a mass spectrophotometry and Nuclear magnetic resonance methods test by an independent laboratory, Eurofins Scientific Inc., Nutrition Analysis Center, 2200 Rittenhouse Street, Ste 150, Des Moines, IA, 90321. www.eurofinsus.com

Please call us at (877) 444-1133 if you would like to discuss further.

Q. What is the osmolarity value and Sodium content of McGuff Compounding Pharmacy’s Ascorbic Acid Injection non-corn 500 mg/mL preservative free?

5.94 mOsm/mL, Na= 61.5 mg

Q. The solution from one ascorbic acid vial has a darker hue than another ascorbic acid vial, why?

Each lot of Ascorbic Acid raw material is tested to prove its origin meets McGuff requirements, in addition to random testing to insure compliance with USP standards. Every lot of Ascorbic Acid Injection non-corn compounded by McGuff is tested for sterility, endotoxin, visual particulate, potency and impurity prior to release. Each step in our compounding process is performed to assure consistency of the drug from lot to lot.

The color of the ascorbic acid raw material powder can vary slightly from one lot to another. Depending on the starting raw material and process, the color of the final Ascorbic Acid Injection can vary from almost no color, to very light yellow or have a yellow tint. This variance is normal and does not affect potency.

Q. Will the combination of Selenium and Ascorbic Acid have an adverse chemical interaction?

According to the references below, selenious acid (selenium) a strong oxidizing agent, and ascorbic acid a strong reducing agent, are chemically incompatible and we recommend not admixing the two products together. References:

http://selenium.atomistry.com

http://selenium.atomistry.com/selenious_acid.html

http://ebm.sagepub.com/content/35/2/231

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Additionally, According to McGuff’s laboratory test results, aqueous selenious acid (which is present in compounded Selenium 200 mcg/mL 30mL MDV) is readily converted to solid elemental selenium (red in color) by a reducing agent, such as Ascorbic Acid, through an oxidation-reduction reaction.

McGuff’s tested the addition of 0.01 mL of Ascorbic Acid Injection 500mg/mL, a reasonable dosing amount, to a vial of selenium 200 mcg/mL, MDV. This resulted in visible orange-pinkish precipitation within minutes.

Q. Will the combination of 5-Multi-Trace Element (MTE), or 4-MTE, and copper-containing mineral product and Ascorbic Acid have an adverse chemical interaction?

MTE-5, MTE-4, both contain copper for injection:

McGuff’s testing has shown that any copper-containing mineral trace element mixture will react with an antioxidant, e.g. ascorbic acid injection, and results in a brown precipitate. We believe that the brown precipitate could be cupric [copper (+2)] turning into cuprous [copper (+1)] and/or ascorbic acid turning into dehydroascorbic acid.

References:

http://pubs.rsc.org/en/Content/ArticleLanding/1988/DT/DT9880000733

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878184/

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Comments:

The intensity/visibility of this chemical reduction-oxidation reaction depends on the I.V. protocol, the quantity of the ingredients, the order of adding the ingredients, the total final volume of the admixture, and possibly the clinician’s technique. The intensity/visibility and color of this interaction can be masked by the amount of ingredients added and/or the total final volume of the admixture. However, the interaction can occur chemically as long as copper, and ascorbic acid are present whether it is visible or not.

Allwood reported on the extent and rate of ascorbic acid decomposition in parenteral nutrition composed of amino acids, dextrose, electrolytes, and trace elements in 3-L PVC bags, stored at 3 – 7 degrees C. About 30 – 40 % of ascorbic acid was lost in 24 hrs. The degradation then slowed as the oxygen supply was reduced by diffusion through the bag. About 50 – 65 % loss occurred after 7 days of storage at 3 – 7 degrees C. The oxidation of ascorbic acid was catalyzed by metal ions, especially copper. In the absence of copper from the trace elements additive, less than 10% degradation of ascorbic acid occurred in 24 hours. The author estimated that 150 to 200 mg is degraded in 2 to 4 hours at ambient temperature in the presence of copper but that only 20 to 30 mg is broken down in 24 hours without copper. To minimize ascorbic acid loss copper must be excluded.

Reference:

Trissel’s Handbook on Injectable Drugs, 13th and 15th Edition. Page 157.

Allwood MC. Factors influencing the stability of ascorbic acid in total parenteral nutrition infusions. J Clin Hosp Pharm. 19984; 9:75-85.

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