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How many units on a U-40 insulin syringe is a 15 mg dose at 10 mg/mL?

Asked 15 May 2024Modified 22 months agoViewed 50k times
31

What I am working with: a U-40 insulin syringe · 15 mg · 10 mg/mL.

I have worked this out and I would like someone to find the error, because I suspect there is one.

My working so far, for the record, is below, and I am fairly sure the error is in the unit conversion rather than the algebra.

How many significant figures are actually justified here?

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DC
askeddrawn_and_capped15k2815 May 2024
5For what it is worth, my own result was within half a per cent of this. – pip_okonjo 9 months ago
4Any reason this would differ for a longer peptide? – lyoph_cake 8 months ago
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5 Answers

Accepted answer first, then by votes
107

Accepted answer

The single most useful thing to do is write the arithmetic on the vial label, because you will reconstruct it from memory at an inconvenient moment if you do not.

Number of stopper piercings matters less than the gauge doing the piercing. A 30G or 31G needle through a butyl stopper leaves a track that reseals; a 21G or 18G drawing needle punches a core and can drop it into the solution.

Reading a lyophilised cake

AppearanceInterpretationAction
Intact opaque puck, proud of baseCycle ran correctlyProceed
Slumped to one sideShipped before fully dry, or vibrationUsually usable; note it
Glassy translucent filmCollapse above glass transitionTest before use
Melt-back ring at stopperThermal excursion in transitTest before use
No visible cake at allVery low fill, or nothing thereWeigh it; query the supplier

Breaking it down further: if a 10 mg vial has 96.5 per cent content, you have 9.65 mg of peptide. Divide that by 2.00 mL and your concentration is 4.825 mg/mL, not 5.00 mg/mL, which is a 3.5 per cent systematic error in every dose calculation.

Published data on syringe dead space quantifies low-dead-space designs as retaining under 2 µL against 35 µL or more for conventional detachable-needle syringes.

I would flag the obvious failure mode: people get the concentration right, get the volume right, and then read the syringe against the wrong scale.

Do the arithmetic twice, ideally with someone else doing it independently.

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YM
answered · acceptedyuki_morishita19k1819 Aug 2024
6I would add a sentence about sterility here, since it is the thing people skip. – e_dziedzic 10 months ago
5The placebo-arm figure is the part everyone omits. – ilaria_bertone 8 months ago
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41

Put another way, the distinction that resolves most of these questions is understanding what concentration actually means and why it is not the same as label claim.

Worked example, because the general form is easier to trust once you have seen it once. Take a 10 mg vial and add 2 mL of diluent: the concentration is 10 ÷ 2 = 5 mg/mL. A 0.5 mg dose is 0.5 ÷ 5 = 0.1 mL. On a U-100 syringe, where 1 unit = 0.01 mL, that is 0.1 ÷ 0.01 = 10 units. Change the diluent to 1 mL and the same dose becomes 5 units — same dose, half the resolution.

The concentration you actually work with is label claim times content fraction divided by actual diluent volume, which is usually not the same as the nominal concentration because content is usually not 100 per cent and you rarely measure the diluent volume to 0.1 mL precision.

The Arrhenius relationship for drawing kinetics means that cold solution takes noticeably longer to draw than room-temperature solution.

The caveat is that this assumes the vial contains what the label says, and if the content assay has not been done, the arithmetic is precise about an unknown quantity.

Write the arithmetic on the vial label. It costs nothing and removes the step where you reconstruct it from memory.

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DW
answeredDr_Elias_Weiss46k3830 Aug 2024
27

More usefully, the answer depends on exactly which dose and which vial you are asking about, but the method is always the same.

Rotation of injection site is a tolerability measure, not a pharmacokinetic one, but if you are going to do it you might as well do it right.

Concretely, air bubbles at these volumes are a measurement problem rather than a safety one. A 2 mm bubble in a 0.3 mL syringe is roughly 4 µL, which at 10 units drawn is a four per cent error.

The content assay results from major testing services show that nominal vial claim and measured content differ by one to ten per cent, making content a driver of dose error.

If in doubt, use more diluent and accept the shorter usable window.

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ED
answerede_dziedzic87k24825 May 2024
Adding for future readers: the certificate should carry the lot number, not just a batch code. – Dr_Priya_Raghunathan 3 months ago
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19

Put another way, work in the order concentration, then volume, then units, and the arithmetic stops being confusing. Concentration is milligrams per millilitre and comes from the vial contents and the diluent volume. Volume per dose is dose divided by concentration. Units on a U-100 syringe are volume in millilitres multiplied by one hundred.

The rounding error accumulates if you round too many times — rounding concentration to 5.0, rounding the dose volume to 0.1 mL, rounding the unit reading to 10 — and the safest approach is to work the full precision and round only the final answer.

The insulin-unit standard U-100 means 100 units per millilitre, so one unit is 0.01 mL — this is the conversion that trips up more people here than any other single piece of arithmetic.

Do the arithmetic twice, ideally with someone else doing it independently.

edited 14 Jun 2024 by coldpack_88 — added the citation requested in comments

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C8
answeredcoldpack_8837k385 Jun 2024
4I would gently push back on the second point — the evidence there is thinner than stated. – Dr_Idris_Coulibaly 10 months ago
5Adding for future readers: the certificate should carry the lot number, not just a batch code. – Dr_Priya_Raghunathan 41 days ago
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-1

Stated carefully, this is arithmetic, so let us do the arithmetic rather than argue about it.

Room temperature before drawing is worth the ten minutes. Cold solution is more viscous, draws slower, and condensation on a cold barrel makes it harder to read the meniscus.

Published data on syringe dead space quantifies low-dead-space designs as retaining under 2 µL against 35 µL or more for conventional detachable-needle syringes.

The limitation is that technique reduces risk, it does not remove it, and nothing you can do outside a controlled environment makes a non-sterile preparation sterile.

Write the arithmetic on the vial label. It costs nothing and removes the step where you reconstruct it from memory.

edited 26 Sept 2024 by ilaria_bertone — added the method parameters

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IB
answeredilaria_bertone43k3811 Sept 2024

Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

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