Good question, well framed, and I would like to see it answered properly.
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Practice · Reconstitution · continued
Coming back to: Over-dilution: when your dose falls below one readable graduation posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Collapsed as off-topic by two members at trust level 3 or above
The arithmetic in post #60 is right; the assumption feeding it is the part to check.
Arithmetic step by step: a 5 mg vial with 2 mL of diluent gives (5 mg) / (2 mL) = 2.5 mg/mL. On a U-100 syringe at that concentration, 100 units = 1 mL = 2.5 mg, so each unit = 0.025 mg. A 0.25 mg dose = 0.25 / 0.025 = 10 units. Different concentration: different arithmetic, same principle.
That is the honest state of it as of this week.
m.coelho, post #58: On Over-dilution: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one. Go to post
Adding what did not work for me on Over-dilution, since the failures never get written up and they are half the useful information.
Worked example, since the arithmetic is the whole question. Five milligrams into one millilitre is 5 mg/mL. A 0.25 mg dose is 0.05 mL, which is five units on a U-100 syringe. Check that against your own numbers rather than taking mine.
Marking that as an opinion rather than a finding.
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f.novak, post #55: Post #54 answers the question as asked. The question underneath it is different. Arithmetic step by step: a 5 mg vial with 2 mL of diluent gives (5 mg) / (2 mL) = 2.5 mg/mL. On a U-100 syringe at that concentration, 100 units = 1 mL = 2.5 mg, so each unit = 0.025 mg. A 0.25 mg dose = 0.25 / 0.025 = 10 units. Different concentration:… Go to post
Post #65 and I disagree about the size of the effect, not about the direction.
Do not shake. Swirl, or leave it. Vigorous agitation introduces air and shear, and neither helps a peptide go into solution any faster than patience does.
A single observation, in a thread that deserves better than single observations.
c.ostergaard, post #4: I changed my mind about Over-dilution after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens. Go to post
The reason Over-dilution is hard to answer is that the obvious measurement and the relevant quantity are not the same thing, and substituting one for the other is silent.
f.novak, post #55: Post #54 answers the question as asked. The question underneath it is different. Arithmetic step by step: a 5 mg vial with 2 mL of diluent gives (5 mg) / (2 mL) = 2.5 mg/mL. On a U-100 syringe at that concentration, 100 units = 1 mL = 2.5 mg, so each unit = 0.025 mg. A 0.25 mg dose = 0.25 / 0.025 = 10 units. Different concentration:… Go to post
Sensible. I would want the same detail before I acted on it either.
m.lindqvist, post #1: Over-dilution: when your dose falls below one readable graduation Writing it up because I had to work it out twice and would rather nobody else did. I have read the maintained page on this and I still have a gap, so I am asking rather than guessing. Context: semaglutide, 7 weeks in, currently at a dose I reached by the standard… Go to post
I read post #70 twice before replying, because I had assumed the opposite.
Preservative effectiveness is tested against a defined microbial challenge under defined conditions. It is not a licence to treat an entered vial as sterile indefinitely, and no supplier claims otherwise.
Stating my assumptions rather than smuggling them in.
I keep a log for Over-dilution specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.
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Research-use-only material reconstituted at home is not a compounded sterile preparation and nothing about the procedure makes it one. Members describing what they do are not describing a pharmaceutical process.
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d.bakker, post #66: Narrowing post #65, because the general version has more than one answer. The claim about Over-dilution upthread is stronger than its source supports. I have read the source. The source says "associated with" and the post says "causes". Go to post
Post #72 is right about the mechanism and I think understates the practical bit.
Preservative effectiveness is tested against a defined microbial challenge under defined conditions. It is not a licence to treat an entered vial as sterile indefinitely, and no supplier claims otherwise.
One more caveat and then I will stop qualifying: the sample selected itself.
For anyone finding this later: the short answer on Over-dilution is that it depends on one thing, and the rest of the thread is people identifying which thing.
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On a U-100 insulin syringe, one hundred units is one millilitre and one unit is 0.01 millilitres. Units are volume marks. They mean nothing until you know the concentration.
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Choose the concentration so that a typical dose lands on a graduation you can actually read. A dose that falls between two marks on a 1 mL barrel is a dose you will get wrong sooner or later.
I keep a log of this specifically because memory is unreliable about it.
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s.teixeira, post #77: On a U-100 insulin syringe, one hundred units is one millilitre and one unit is 0.01 millilitres. Units are volume marks. They mean nothing until you know the concentration. Go to post
A request rather than an answer: could whoever has the primary source for Over-dilution post it? I have seen the claim three times this month and each version had lost a qualifier.
Clear enough that I do not think I have a follow-up, which is unusual.
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Helpful, and short, which on this subject is harder than long.
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If your arithmetic gives a volume smaller than one graduation on your syringe, the answer is a lower concentration rather than a more careful hand.
I would be glad to be shown a cleaner way of putting this.
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i.amankwah, post #71: Sensible. I would want the same detail before I acted on it either. Go to post
Swirling until fully clear before drawing is worth the extra minute. A partially dissolved preparation is not uniform and the first dose out of it is not the same as the last.
The confident version of this sentence would be wrong, so here is the hedged one.
Dead volume is the part nobody mentions until it costs them a dose. A fixed-needle insulin syringe holds very little; a detachable-needle luer configuration can hold enough to matter at small doses.
I am not the right person to answer the follow-up to this.
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Answering the question post #83 raises rather than the one it answers.
Worth separating Over-dilution as a question about the compound from Over-dilution as a question about the documentation. They get answered by different people and only one of them is answerable here.
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d.bakker, post #66: Narrowing post #65, because the general version has more than one answer. The claim about Over-dilution upthread is stronger than its source supports. I have read the source. The source says "associated with" and the post says "causes". Go to post
Where I have landed on Over-dilution, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.
forest_plot, post #28: Useful. I had the fact and not the reason, which turns out to be the important half. Go to post
On post #87 — agreed on the reasoning, with one qualification.
The best check on any reconstitution calculation is to do it twice by two different routes — mass per volume, then volume per dose — and see whether they agree. They should, and when they do not it is nearly always the concentration step.
Anyone who has looked at this more carefully, please correct the record.