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Pernicious Anaemia Society
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Sourcing and storage of Saline solutions of Methylcobalamin

I have intermittently come across concerns on this site regarding the supply and thermal/photo stability of saline solutions of methyl cobalamin.

Since I wanted to source a saline solution myself I thought the following information would be of general interest.

1. Having been unimpressed by sourcing in the UK I approached Arnika in Germany and found that they will take an order in English by email without any registration by way of this email address. Payment was made via email/Paypal. Delivery was a few days.

Manufaktur@arnika-apo.de

Service was excellent

2. After much literature searching the following reference allayed my concerns regarding storage of the ampoules

researchgate.net/publicatio...

Stability of high-dose methylcobalamin injection

Article in Journal of Applied Therapeutic Research 6(3):15-18 · January 2008 with 665 Reads

• C. Kusadome

• Y. Shibayama

• Y. Nishi

• Yasuo Takeda

◦ 36.97

◦ Kagoshima University

Show more authors

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. It is treated with an active form of vitamin B12, methylcobalamin (mecobalamin). Recently, it has been reported that high-dose treatment with methylcobalamin may delay the progression of ALS. We have manufactured high-dose injections of methylcobalamin as a hospital formulation; however, the stability of the injection was unclear. Here we examined the stability of the injection using high performance liquid chromatography (HPLC). Methylcobalamin solution (12.5mg/ml, diluted with saline) was sealed in a brown glass ampoule under dark conditions (1-2 lux). The ampoules were sterilized by autoclaving (115°C, 30 minutes), and then protected from light with aluminum foil. After the ampoules had been kept under cool conditions (4°C) for 3 months, the concentration of methylcobalamin was found to be 96.4 ± 2.4% (mean ± S.E.) of the control value. After 6 months, methylcobalamin had decreased to 91.6 ± 1.4% (mean ± S.E.). In contrast, methylcobalamin quickly degenerated to 49.9 ± 8.2% (mean ± S.E.) of the control after only four hours' exposure to bright light (1,000 lux). In conclusion, the results suggest that injections of high-dose methylcobalamin can endure an autoclave, but methylcobalamin rapidly deteriorates with exposure to light. Thus, high-dose methylcobalamin injections should be prepared under dark conditions to prevent light-dependent degeneration.

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"After the ampoules had been kept under cool conditions (4°C)"

This is the bit that cowboy importers ignore. They will tell you that it doesn't need refrigeration. Indeed, one UK supplier says that it doesn't need refrigeration - and include a patient information leaflet that says it needs to be kept below 5 C.

Just for interest - how much was it?

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39.90 euros plus 15 euros delivery charges for 10 x 1ml ampoules containing 5mg each This was a better deal per mg of methyl cobalamin than buying 10 x 1ml ampoules containing 1mg each.

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100 ampoules of hydroxocobalamin (1 mg) is only €57 inc. postage. That works out at €0.57 per mg (and €0.57 per injection). Your methylcobalamin is €1.10 per mg (and €5.40 per injection).

That seems to be a lot for a form of B12 that is no more effective, possibly less effective, and a lot less stable that hydroxocobalamin.

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With respect we should compare like with like. I also have bought hydroxocobalamin 1mg in 1ml ampoules in a clinical pack of 100 which indeed worked out at ca €57 inc postage.

The methylcobalamin that I purchased recently cost €54.90 for 10 amber coloured ampoules of 5mg in 1ml each. When required I subdivided each ampoule into 5x 0.2ml sterile insulin syringes which I resealed and immediately wrapped in aluminium foil syringes and kept in a cool place. All done with careful attention to cleanliness (wiped surfaces with antibacterial spray etc). My dosing regime was 1mg ie 0.2ml every other day so they were stored 1.5 week max.

The overall cost per 1mg injection was therefore €1.10 compared to €0.57 for 1mg of hydroxocobalamin. Alternatively they offered 10x 1mg in a 1ml ampoules at €44.90 which works out at €4.49 per 1mg injection.

My own research opposite the efficacy of methylcobalamin led me to the conclusion that it's probably 'horses for courses' and a diagnostic 50x doses every other day would convince me one way or the other, whether it could improve my own long standing neurological symptoms.

Regarding the stability of the solutions I will reply to Elijahhawk with my findings.

Thank you both for your comments, it's my first blog here.

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As soon as the methylcobalamin enters the cell the methyl group is removed leaving cob(II)alamin. As soon as hydroxocobalamin enters the cell the hydroxyl group is removed leaving cob(II)alamin. As soon as cyanocobalamin enter the cell the cyano group is removed leaving cob(II)alamin.

ncbi.nlm.nih.gov/pubmed/258...

All forms of B12 are converted to cob(II)alamin as soon as they enter the cell.

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I agree with what you have said but there still remains the possibility in my mind that the methylcobalamin TC complex which passes through the cell wall may do so at a different rate to the hydroxocobalamin TC complex which is what passes through the cell wall in people not supplementing with methylcobalamin. There is also the consideration that different cells in the body may accept these two cobalamin TC complexes more or less readily to each other. That's why I decided to do a diagnostic trial.

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The two best articles I have found to explain the complicated B12 story are

bloodjournal.org/content/11...

bloodjournal.org/content/12...

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Yes, I am familiar with the first of those and it’s very good.

I wasn’t familiar with the second, but it is also good. Some bits I really like are...

“Where the cause of the deficiency is not known or irreversible, treatment must be lifelong.”

And

“It should be noted that patients with pernicious anemia at times report that the recommended treatment schedule is not adequate to relieve all their neurological symptoms and therefore often request, or may even treat themselves with, B12 injections more frequently than the guidelines suggest. No biological basis for this apparent increased requirement for B12 replacement is known, but because there are no reports of adverse effects associated with excess B12 intake, there is no reason to advise against this practice.“

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I receive Methylcobalamin (premeasured syringes) from a reputable compounding pharmacy here in the U.S.

I was intially concerned about the way that they shipped it. It comes packaged in a styrofoam container packed between two ice packets.

It's frozen and intended to stay that way until unthawed for use.

I have read conflicting things about how it was to be kept, so I spoke with the pharmacist that prepares it. She told me that it is tested for potency after having been frozen and that it maintains full potency for 45 days. Beyond that, she didn't know because they never had it tested for anything longer.

It is also sent in a bag that light cannot penetrate. And for each syringe that needs to be unthawed, a separate pouch is sent to allow it to be unthawed protecting from exposure to light.

She also said that leaving it on the counter to unthaw and not protected from light can degrade it about 5% in just 10 minutes.

Having said all of that, I guess I would go on the recommendations of those that manufactured it.

It does need to be kept cool/frozen and no contact with light.

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