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Why is my second draw from the same vial reading a different volume?

Asked 1 Sept 2024Modified 20 months agoViewed 46k times
24

I keep a written log of every draw with date, volume and syringe type.

Something has gone wrong and I would like to know how badly before I decide what to do.

Nothing else in the setup changed, which is what makes this puzzling.

What is the differential here, and which test discriminates between the options?

insulin-syringe
insulin-syringe

U-100 and U-40 insulin syringes as measuring instruments. A U-100 syringe is graduated in insulin units where 100 units equals 1 mL, so one unit…

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dead-space
dead-space

The volume trapped in the syringe hub and needle after the plunger bottoms out. It is small in absolute terms and large as a fraction of a small…

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dosing-math
dosing-math

The arithmetic itself: milligrams to millilitres to insulin units, concentration after reconstitution, dose per draw, and vial-days per vial. Show…

811 questions
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DW
askeddeamidation_watch43k381 Sept 2024

5 Answers

Accepted answer first, then by votes
143

Accepted answer

Worth being precise here: 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.

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.

Dead space by syringe type

ConfigurationDead volumeLoss at 5 mg/mLOver 20 draws
Fixed-needle insulin syringe3–5 µL15–25 µg0.3–0.5 mg
Low-dead-space, detachable<2 µL<10 µg<0.2 mg
Standard luer-lock + 30G35–60 µL175–300 µg3.5–6 mg
Luer-lock + 21G drawing needle70–100 µL350–500 µg7–10 mg

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

Worth noting: the concentration after reconstitution is not the same as the label claim, and most people do not account for the difference.

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

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answered · acceptedp_mkhize41k13814 Nov 2024
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58

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

On filtration: a 0.22 µm syringe filter will remove particulates and organisms, and it will also adsorb a fraction of your peptide onto the membrane — with a low-binding PVDF or PES membrane the loss is typically a few per cent.

It helps to be literal here: 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.

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.

One qualification: if your arithmetic and someone else's disagree by a factor of ten, one of you has made a unit error, and writing out the units at every step is the diagnostic.

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

edited 12 Nov 2024 by shear_at_the_front — fixed an arithmetic slip in the third paragraph

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SF
answeredshear_at_the_front15k283 Nov 2024
41

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.

Do not use the same needle to pierce the stopper and to administer. The tip is blunted by the stopper, and the hub now contains a dose you are about to lose to dead space anyway.

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.

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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LS
answeredlukas_sedlacek17k2723 Oct 2024
34

To be exact about it, dose arithmetic has three parts: concentration from vial content and diluent, volume from dose and concentration, and units from volume and syringe scale.

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.

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

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P9
answeredplate_count_9k95k15812 Oct 2024
8This is the first explanation of that which has actually made sense to me. – fiadh_cronin 9 months ago
7Note that the label instructions differ between agents on precisely this point. – Dr_Colm_Fitzhenry 8 months ago
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31

Rounding to the nearest whole syringe unit is usually the right error to make, but understanding which direction it is and why matters.

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.

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

edited 14 Oct 2024 by Dr_Ilse_Vandenberg — reworded for clarity after a comment

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DV
answeredDr_Ilse_Vandenberg78k2481 Oct 2024
8Any reason this would differ for a longer peptide? – e_dziedzic 38 days ago
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