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Practice · Reconstitution

Second pass at: Choosing a concentration on purpose rather than by accident

SD
s.dziedzicTL2 Moderator28 Oct 2024#1

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.

Practical question with the units stated, because I have seen how quickly these go wrong without them.

I have a 2 mg vial of semaglutide and I am working to a 2.5 mg step. My syringes are U-100 insulin syringes, 0.3 mL barrel.

I can do the arithmetic and I have done it twice, getting the same answer both times, but I would like someone to check the reasoning rather than the number — specifically whether I have thought about the residual volume correctly, and whether the graduation I am landing on is one a person can actually read.

0 likes 21mo
NK
ni.kravchenkoTL2 Moderator30 Oct 2024 · edited#2

Swirling versus inverting versus leaving it alone: the vial can be gently warmed (hands around it) and swirled with a rolling motion. Vigorous shaking introduces air and can denature the peptide. Leaving it alone at room temperature usually works given enough time.

24 likes 21mo
EA
e.almeidaTL2Member1 Nov 2024#3

I read the opening post twice before replying, because I had assumed the opposite.

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.

7 likes 21mo
RS
r.sobczakTL2 Moderator3 Nov 2024#4
s.dziedzic, post #1: 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. Practical question with the units stated, because I have seen how quickly these go wrong without them. I have a 2 mg vial of semaglutide and I am working to a 2.5 mg step. My… Go to post

Osmolarity and reconstitution: the osmolarity of the reconstituted solution affects comfort on injection. Isotonic solutions (close to blood osmolarity) are less irritating than hypertonic solutions. This is why diluent choice (sterile water vs. saline) matters.

1 like in reply to #1 21mo
I
IHollingworthTL2Member4 Nov 2024#5

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.

0 likes 21mo
NR
n.ramosTL2 Moderator5 Nov 2024#6

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

17 likes 21mo
LS
l.sarkissianTL2Member7 Nov 2024#7

Coming back to post #5, because the follow-up matters more than the original answer.

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.

4 likes 21mo
TM
t.marchettiTL2 Moderator8 Nov 2024#8
e.almeida, post #3: I read the opening post twice before replying, because I had assumed the opposite. 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

Picking up post #5: that is the part I would want checked first.

Foaming during reconstitution: bubbles in the solution are usually just air incorporated during mixing. They usually resolve with gentle warming and time. Persistent foam is unusual and might warrant contact with the supplier, but initial foam is ordinary.

0 likes in reply to #3 21mo
P
PWendelboeTL1Member9 Nov 2024 · edited#9
ni.kravchenko, post #2: Swirling versus inverting versus leaving it alone: the vial can be gently warmed (hands around it) and swirled with a rolling motion. Vigorous shaking introduces air and can denature the peptide. Leaving it alone at room temperature usually works given enough time. Go to post

Worth separating two things that post #5 runs together.

Why "add 2 mL" is not an instruction: the powder in the vial takes up space. "Add 2 mL to a 10 mL vial" and "add 2 mL of diluent so the final volume is approximately 2 mL" are different instructions. Stating the final target volume is clearer than stating the diluent added.

1 like in reply to #2 21mo
CN
c.nybergTL2 Moderator10 Nov 2024#10
PWendelboe, post #9: Worth separating two things that post #5 runs together. Why "add 2 mL" is not an instruction: the powder in the vial takes up space. "Add 2 mL to a 10 mL vial" and "add 2 mL of diluent so the final volume is approximately 2 mL" are different instructions. Stating the final target volume is clearer than stating the diluent added. Go to post

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.

0 likes in reply to #9 21mo
RC
r.coelhoTL2 Moderator11 Nov 2024#11
c.nyberg, post #10: 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. Go to post

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.

9 likes in reply to #10 21mo
BP
bench_peakTL3Regular12 Nov 2024#12
e.almeida, post #3: I read the opening post twice before replying, because I had assumed the opposite. 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

On post #8 — agreed on the reasoning, with one qualification.

The decimal-point error: computing 5 mg / 2 mL as 0.25 mg/mL instead of 2.5 mg/mL is the most common arithmetic error in this subcategory. The habit that catches it: writing the units in every step of the calculation.

21 likes in reply to #3 20mo
MN
m.ndiayeTL2 Moderator13 Nov 2024#13

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.

0 likes 20mo
HK
h.kjeldsenTL1Member14 Nov 2024#14

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.

2 likes 20mo
SO
s.okonkwoTL2 Moderator15 Nov 2024#15

post #14 is right about the mechanism and I think understates the practical bit.

Foaming during reconstitution: bubbles in the solution are usually just air incorporated during mixing. They usually resolve with gentle warming and time. Persistent foam is unusual and might warrant contact with the supplier, but initial foam is ordinary.

5 likes 20mo
CD
cohort_driftTL3Regular17 Nov 2024#16
IHollingworth, post #5: 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. Go to post

Worth separating two things that post #12 runs together.

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.

14 likes in reply to #5 20mo
TV
to.vargaTL2 Moderator18 Nov 2024 · edited#17

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

0 likes 20mo
SS
stopper_shiftTL1Member19 Nov 2024#18

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.

0 likes 20mo
ND
n.dziedzicTL2 Moderator19 Nov 2024#19
r.sobczak, post #4: Osmolarity and reconstitution: the osmolarity of the reconstituted solution affects comfort on injection. Isotonic solutions (close to blood osmolarity) are less irritating than hypertonic solutions. This is why diluent choice (sterile water vs. saline) matters. Go to post

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

20 likes in reply to #4 20mo
J
JFitzgibbonTL2Member20 Nov 2024#20

Swirling versus inverting versus leaving it alone: the vial can be gently warmed (hands around it) and swirled with a rolling motion. Vigorous shaking introduces air and can denature the peptide. Leaving it alone at room temperature usually works given enough time.

0 likes 20mo
D
DOdendaalTL3Regular21 Nov 2024#21

Worth separating two things that post #17 runs together.

Osmolarity and reconstitution: the osmolarity of the reconstituted solution affects comfort on injection. Isotonic solutions (close to blood osmolarity) are less irritating than hypertonic solutions. This is why diluent choice (sterile water vs. saline) matters.

13 likes 20mo
DV
d.vestergaardTL2 Moderator22 Nov 2024#22

post #21 is right about the mechanism and I think understates the practical bit.

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.

5 likes 20mo
SF
sterile_fileTL3Regular23 Nov 2024#23
m.ndiaye, post #13: 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. Go to post

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.

0 likes in reply to #13 20mo
CM
c.marchettiTL2 Moderator24 Nov 2024#24
t.marchetti, post #8: Picking up post #5: that is the part I would want checked first. Foaming during reconstitution: bubbles in the solution are usually just air incorporated during mixing. They usually resolve with gentle warming and time. Persistent foam is unusual and might warrant contact with the supplier, but initial foam is ordinary. Go to post

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

0 likes in reply to #8 20mo
AS
a.stephanopoulosTL3Regular25 Nov 2024#25

The decimal-point error: computing 5 mg / 2 mL as 0.25 mg/mL instead of 2.5 mg/mL is the most common arithmetic error in this subcategory. The habit that catches it: writing the units in every step of the calculation.

9 likes 20mo
LC
l.cabreraTL2 Moderator26 Nov 2024#26

post #25 answers the question as asked. The question underneath it is different.

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.

2 likes 20mo
VM
v.milanoviTL3Regular27 Nov 2024 · edited#27
bench_peak, post #12: On post #8 — agreed on the reasoning, with one qualification. The decimal-point error: computing 5 mg / 2 mL as 0.25 mg/mL instead of 2.5 mg/mL is the most common arithmetic error in this subcategory. The habit that catches it: writing the units in every step of the calculation. Go to post

Coming back to post #25, because the follow-up matters more than the original answer.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

0 likes in reply to #12 20mo
FP
f.petrovTL2 Moderator28 Nov 2024#28

Why "add 2 mL" is not an instruction: the powder in the vial takes up space. "Add 2 mL to a 10 mL vial" and "add 2 mL of diluent so the final volume is approximately 2 mL" are different instructions. Stating the final target volume is clearer than stating the diluent added.

28 likes 20mo
BE
bench_entryTL3Regular29 Nov 2024#29

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.

5 likes 20mo
IW
i.wojcikTL230 Nov 2024#30