Second pass at: Choosing a concentration on purpose rather than by accident Writing it up because I had to work it out twice and would rather nobody else did.
Posting a small dataset on Choosing a concentration. It is mine, it is uncontrolled, and the method is stated so it can be discounted appropriately.
What I would like is not agreement but a second dataset collected by someone with no stake in mine. If one exists I would rather read it than argue for this one.
Bookmarking this. I will come back when I have something worth adding.
I had written a reply contradicting the opening post and deleted it. Here is what survived.
Reconstituting a multi-strength kit: if a kit contains 5 mg, 10 mg, 15 mg vials and you are reconstituting all of them, writing the concentration on each vial in permanent marker as you go is the single most useful thing you can do to avoid dose errors later.
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.
Two claims get bundled together under Choosing a concentration and they need separating. The descriptive one — this is what was observed — is usually well supported. The causal one — this is why — usually is not.
Almost every disagreement in threads like this one dissolves once you say which of the two you are making.
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.
Worth checking against a second source before it gets quoted onward.
Where I part company with post #5, and it is a narrow parting.
How much of the diluent volume the powder itself displaces: for a small peptide vial, the powder volume is negligible. For a larger vial or a kit with multiple compounds, the displacement can be a few tenths of a millilitre. If precision matters to you, account for it by targeting a final weight rather than a final volume.
Second-hand, so weight it accordingly.
Post #5 is the version of this I will quote in future. One addition.
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.
Post #5 and I disagree about the size of the effect, not about the direction.
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.
Over-dilution: if your target dose is 0.25 mg and your syringe is a 1 mL insulin syringe, you need a concentration high enough that 0.25 mg fits on the scale. A 0.25 mg/mL solution requires drawing the entire 1 mL syringe — not readable. A 5 mg/mL solution requires drawing 50 μL — also not practical on an insulin syringe.
Working out the concentration after the fact from the volume you added is fine. Working it out from the volume you meant to add is where the errors come from — read the barrel, not the plan.
Not a conclusion. A place to stand while looking for one.
Coming back to post #8, because the follow-up matters more than the original answer.
Add the diluent down the side of the vial rather than directly onto the cake. It is slower and it avoids the foaming that makes people think something has gone wrong.
If anyone has run this properly I would rather read that than my own guess.
A vial that will not fully dissolve: check in order: is the diluent genuinely room temperature (some preservatives crystallise in cold), is the vial being warmed gently rather than shaken hard, is the injection technique clean, is the vial integrity intact. Work through that checklist before concluding the powder is insoluble.
I think the Choosing a concentration question is answerable and has not been answered, which is a more optimistic position than most of this thread.
Post #14 answers the question as asked. The question underneath it is different.
A cake that takes a few minutes to dissolve is ordinary. A cake that will not dissolve after gentle swirling and standing at room temperature is worth raising with the supplier rather than working around.
Two people can read the same figure differently here and both be reasonable.
I read post #12 twice before replying, because I had assumed the opposite.
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.
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.
One of those cases where knowing the mechanism does not help the decision.
I would rather this thread reach "we do not know" about Choosing a concentration than reach a confident answer that nobody can support when asked.
On Choosing a concentration, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.
If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.
Narrowing post #21, because the general version has more than one answer.
The reason Choosing a concentration 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.
Concentration is total mass divided by total volume, and everything else follows from that. Ten milligrams into two millilitres is five milligrams per millilitre, and it does not matter how the vial was labelled before you added anything.
The step people skip is the one I have spelled out.
Write the reconstitution date and the concentration on the vial. Not on a note, on the vial. Every account here of a dosing error involving the wrong concentration involves a vial with nothing written on it.
That much is documented. The rest is how I have interpreted it.
What I would check first on Choosing a concentration is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
Post #25 answers the question as asked. The question underneath it is different.
Choosing a concentration on purpose rather than by accident: starting with "I want to draw 0.5 mL per dose" and working backward to the required concentration is more efficient than picking a diluent volume and hoping the math works out. State your target volume, then the required concentration follows.
No notes. Posting so the count is not one.
A 10 mg vial reconstituted three different ways: 1 mL diluent gives 10 mg/mL, 2 mL gives 5 mg/mL, 4 mL gives roughly 2.5 mg/mL. The arithmetic is the same; the concentration determines which syringe graduations are legible.
I checked the source rather than the summary, and they differ.
Working out the concentration after the fact from the volume you added is fine. Working it out from the volume you meant to add is where the errors come from — read the barrel, not the plan.
The strength of my opinion here exceeds the strength of my evidence.
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.
If that is already documented somewhere, ignore me and link it.