Musings on microdosing by weight

[bsmith]

I thought maybe we should move this discussion to its own thread and stop cluttering up the DOSING WITH CALIPERS thread. I'll try to move the bulk of our text over here. (Is there a way to move posts to a different thread?)

Here's the discussion so far. (My text is in regular text or bold and others' replies are in quotes. I reordered the messages by the three replying posters to try to clarify the discussion as I can't just copy the relevant posts from the other thread over here.) Perhaps something will come of this idea, perhaps not.



Has anyone ever tried microdosing by weight? Fairly accurate digital scales (not kitchen type scales, think finer scales for reloading or chemical use) are fairly inexpensive these days. Anyone tried it? Is there enough difference in weight between 0.25 u and 0.5 u of Lantus to accurately dose? If so, you could just weigh the syringe, zero the scale out, and then weigh your dose. That would take the variations between syringes (their marking and different weights) out of the equation.

Just ordered a scale with o.o1 g precision. I hope that will work or I'll try one with 0.001 g precision. Too bad I don't have lab access at this moment or I'd go use one of their fancy scales to figure out the precision I need and if this will work.

Lab-quality scales that can weigh less than 1 mg cost thousands of dollars. If we assume that Lantus has the same density as water (likely it does not), then 1 unit of Lantus (10 microL) would weigh 10 mg. That's not something that a consumer-grade scale could weigh accurately.

100 u Lantus/ml, according to Lantus people (telephone call with transfer to a lab guy) use same density as water 1 g/ml, which gives 1 u =0.01g (10 mg, as you stated, please correct my math if I slipped again as I've had very little sleep lately). So one 1/4 u = 0.0025 g.

The scale I ordered last night was off by an order of magnitude (it was late, I slipped a decimal place), but the one I ordered today will measure to a tolerance of 0.001 g with a large enough platform for the syringe ($23.00 US). I've haven't tried it yet, but "in theory," at least, it should work. For the last 0.0005, you may be able to get close by getting the scale to flip between 0.002 g and 0.003 g (hopefully it will be sensitive enough to do this). I'm hoping this will give better, or at least equal, reliability to using calipers or drop dosing. It's got to be better than my eyeball and magnifying glass method.

Now to see if I have the manual dexterity to do this accurately. For my next trick, I will build a robot to control the plunger of the syringe (just joking). Or perhaps I should start trawling the scientific surplus and used equipment sites for used lab grade scales.

(Just noticed you're from Worcester, MA. I went to grad school there. How's the snow been doing?)

I work in a lab, and when I want to put something in a test tube and get its weight, I put that test tube in a small cup so it stands upright. The scale I use for tiny amounts has 4 digits and can actually go to 5 digits, but I do not trust anything under 1 mg. Knowing that Lantus is similar enough to water in terms of density makes the math easy. You are correct in that 0.25U would be 2.5uL or 2.5 mg. There are glass microsyringes that will accurately measure these tiny volumes, but the problem is they would have to be sterilized after each use, and the needles for them are *not* the itty bitty skinny insulin needles. If someone would just figure out a proper diluent for Lantus that does not affect its chemical properties, all of this microdosing would be a nonissue. I believe some insulins have specific diluents for use in small children, but I don't know of any for Lantus.

Yes, Worcester really got buried this year, and it's not over yet...

I have one of those scales (note: a scale similar to the type of scale that I am buying) that I use for weighing Max's medications since his pills are impossible to cut. I just tried to weigh the syringe but the part where you place what you want to weigh is too small. Every time I tried to weigh the syringe I got different results.

How big is the weighing platform on your scale? The scale that I bought should be large enough to fit the syringes I use, which will help to get more consistent results(I hope). Also, some scales are more accurate than others. Have you ever calibrated your scale? That sometimes helps with accuracy. Although, if it accurately weighs things that do fit on the platform, I wouldn't worry about calibrating it. Thanks for trying it out with the scale you have.

I calibrated the scale when I got it and it works well for the meds. It's the AWS DIA-20. It's supposed to be accurate to 0.001g,

http://wholesale-scales.com/index.php?main_page=product_info&products_id=363

Thanks for showing me what you're using. Since the weighing platform is only 1 3/8" diameter, it would be difficult to balance a syringe firmly on that and get an accurate weight. You could try balancing a card or piece of cardstock on the platform to try to get a larger somewhat more stable platform. See if that helps.

I would imagine the syringes would also vary by weight. They are made by a machine. I think it would twke more time to do what you are proposing but it might be interesting to see what you find.

Thanks. As far as the different weights of individual syringes, that's why you place the empty syringe on the scale first and press the tare/zero button. Then, when you add insulin, the scale automatically subtracts the weight of that particular syringe and shows just the weight of the insulin.

 

[bsmith]

I work in a lab, and when I want to put something in a test tube and get its weight, I put that test tube in a small cup so it stands upright. The scale I use for tiny amounts has 4 digits and can actually go to 5 digits, but I do not trust anything under 1 mg. Knowing that Lantus is similar enough to water in terms of density makes the math easy. You are correct in that 0.25U would be 2.5uL or 2.5 mg. There are glass microsyringes that will accurately measure these tiny volumes, but the problem is they would have to be sterilized after each use, and the needles for them are *not* the itty bitty skinny insulin needles. If someone would just figure out a proper diluent for Lantus that does not affect its chemical properties, all of this microdosing would be a nonissue. I believe some insulins have specific diluents for use in small children, but I don't know of any for Lantus.

Yes, Worcester really got buried this year, and it's not over yet...

I moved this discussion to a thread of its own.

You seem to have a better background in pharmacology (and/or chemistry) and the weighing of small things than I do. How well can you calibrate your scale? It sounds like a really nice one, I'm jealous, so I assume it has all sorts of options for calibration.

I have seen calibration weight sets that include reference weights down to 1 mg. Do you have any experience with this size of reference weights and their reliability? Have you tried using them with your scale? I hope that such reference weights will at least allow me to determine what margin of error I'm dealing with. Perhaps measuring the weight of sample multiple times, and then averaging it, will help get a more accurate result. Of course, by now, this is all starting to sound like a lot work just to get my cat his dose of insulin.

I'm also thinking of using an added reference weight, when trying to weigh 2.5 mg, to get nearer to the center of the scale's range. I would hope the results would be more reliable towards the scale's midrange values. Have you found this to be true for your scale?

Alas for an autoclave of my own. With your microsyringes are you able to measure out those tiny volumes and then remove the needle assembly and draw the liquid out with a standard U100 syringe? I assume not or you would have mentioned it. I also assume that smaller needles are not available for the microsyringes since the small needle gauge would prohibit proper cleaning.

Looking into why Lantus can't be diluted is interesting. Apparently small crystals form at the injection site and this is what gives Lantus its long acting action. Standard dilution keeps these crystals from forming. However, there is a report of Lantus being diluted with saline for use on a newborn (link). Though, as we well know, medications in humans and medications in cats are two different things. It would indeed be helpful to have a diluent that would still allow for the formation of the needed crystals.

 

[BJM]

What you need is a diluent for Lantus which has the same pH and the same density.

 

[Carl & Polly & Bob (GA)]

I thought maybe we should move this discussion to its own thread and stop cluttering up the DOSING WITH CALIPERS thread. I'll try to move the bulk of our text over here. (Is there a way to move posts to a different thread?)

It looks like you were able to copy posts from one condo to another?
I wasn't sure what options are available to non-moderators, but in answer to your question, yes, mods can move posts from one thread to another if you let us know where they are and where they need to be moved.

I have less than no clue about diluting Lantus so I'm no help there

Carl

 

[MJ+Donovan]

This is a 10 uL glass microsyringe. I can't honestly think of a good way to get Lantus from this syringe to an insulin syringe, short of squirting it into the barrel. This particular microsyringe does have a removable needle option, and I did see 31 gauge needles available, so I suppose it is possible to do an injection directly with this syringe. Soaking in ethanol or boiling it ought to be sufficient disinfection if you can't autoclave it.

As I recall, someone here tried using something like this a few years ago, but he got frustrated for various reasons and gave up. He is no longer active on this board. Anyone else remember that?

As for the analytical scale, we do have a set of weights to check it, but we also have it calibrated by a professional about once a year.

If you want to play around with a micropipettor, or some of these glass microsyringes, let me know. We have old microsyringes that we no longer need.

MJ

 

[Jill & Alex (GA)]

What you need is a diluent for Lantus which has the same pH and the same density.

Hmm... maybe, but...

"Glargine is a relatively stable insulin; therefore, it would be expected that it could also be diluted with insulin or saline just before injection. Be aware that it will form a cloudy precipitate in the syringe. Mixing it in the bottle is not recommended because of problems with accuracy and dosing when the insulin is a precipitate, bacterial contamination and the unknown effect on stability and efficacy.
(management of diabetic cats.pdf from Roomp and Rand)

As I recall, someone here tried using something like this a few years ago, but he got frustrated for various reasons and gave up. He is no longer active on this board. Anyone else remember that?

MJ, are these the threads you're thinking of:
Brainstorming thread: How would you design a better syringe?
Review of Hamilton Microliter Syringes

 

[bsmith]

Apparently the updates to this thread have not been popping up in my email box. I'll check my settings.

I thought maybe we should move this discussion to its own thread and stop cluttering up the DOSING WITH CALIPERS thread. I'll try to move the bulk of our text over here. (Is there a way to move posts to a different thread?)

It looks like you were able to copy posts from one condo to another?
I wasn't sure what options are available to non-moderators, but in answer to your question, yes, mods can move posts from one thread to another if you let us know where they are and where they need to be moved.

I have less than no clue about diluting Lantus so I'm no help there

Carl

Just straight up copy and pasting with the appropriate quotations from others. I think what I posted at the beginning is clear enough that we don't have to have a mod move the posts. If my first message, with the copy and pasting, is unclear, please let me know and I'll see about getting the actual posts moved. I was pretty sure the mods had the power to move posts, but was unsure where to ask for that to be done. Would I just post a message on the tech forum?

 

[bsmith]

This is a 10 uL glass microsyringe. I can't honestly think of a good way to get Lantus from this syringe to an insulin syringe, short of squirting it into the barrel. This particular microsyringe does have a removable needle option, and I did see 31 gauge needles available, so I suppose it is possible to do an injection directly with this syringe. Soaking in ethanol or boiling it ought to be sufficient disinfection if you can't autoclave it.

As I recall, someone here tried using something like this a few years ago, but he got frustrated for various reasons and gave up. He is no longer active on this board. Anyone else remember that?

As for the analytical scale, we do have a set of weights to check it, but we also have it calibrated by a professional about once a year.

If you want to play around with a micropipettor, or some of these glass microsyringes, let me know. We have old microsyringes that we no longer need.

MJ

Yeah, I'm unsure how to get the Lantus from that syringe into an insulin syringe other than squirting it into the barrel, as you suggested. I wonder how much would be lost in the transfer and if I could get the majority of the air out of the barrel of the insulin syringe without also losing the Lantus. I suppose letting it sit in the refrigerator and allowing gravity do the work might do the job. Does anyone know how long you are allowed to let Lantus sit in a syringe? I've heard that preloading syringes with Lantus is discouraged.

Are there microsyringes with needles that have inner diameters large enough to get a 30 gauge insulin needle inside of it? Is it possible to pull the insulin out that way? My inexperience with syringes and needles is really showing here.

The 31 gauge needle available for the microsyringe is intriguing. I do enjoy the smell of ethanol in the morning, so that would be a viable way of disinfecting.

I assumed that your scale would have reference weights, but a professional to calibrate it every year is nice. Is your distrust of anything under 1 mg from experience or from known error deviations in the scale's documentation?

If you would be willing to send me a micropipettor and a few microsyringes that would be great. When you are trying things out you only need a few pieces, but many supply companies require you to buy a gross at a time. That's a bit pricey for just trying out something that may not work. PM me and I'll send you my address. If you're not able to ship them yourself (I can send money to cover the shipping cost, if needed), I can probably get a friend in Worcester to come pick up the items.

Thanks for all you help and information.

 

[bsmith]

MJ, are these the threads you're thinking of:
Brainstorming thread: How would you design a better syringe?
Review of Hamilton Microliter Syringes

Thanks for the links. Off to do some reading now.

Edited: The PDF you attached has a table that my vet sent home with me today (Table 2). I've been meaning to look at that paper as I think @BJM has pointed me in its direction before. Thanks for the reference.

 

[julie & punkin (ga)]

Are you thinking you would reweigh every dose once you figured out how much the desired dose weighed? It seems like that would be a ton of work - i can imagine having it weigh a shade too much, then working out too much and having to add more insulin to the syringe. And repeat.

Have you tried calipers yet? I haven't heard anyone complain about them, in fact i think for the most part, people really like them once they get the hang of using them. You set the dose based upon your particular syringes, then just compare the syringe to the caliper arms.

 

[bsmith]

Are you thinking you would reweigh every dose once you figured out how much the desired dose weighed? It seems like that would be a ton of work - i can imagine having it weigh a shade too much, then working out too much and having to add more insulin to the syringe. And repeat.

Have you tried calipers yet? I haven't heard anyone complain about them, in fact i think for the most part, people really like them once they get the hang of using them. You set the dose based upon your particular syringes, then just compare the syringe to the caliper arms.

This thread actually moved over here after starting on the dosing with calipers thread. I was trying to think of a way to get away from variations between syringes (there are variations between syringes from the same manufacturer, even within the same lot - barrel length, needle placement, barrel wall thickness, etc.) and measure the Lantus alone. Dosing with calipers does not take all these manufactured differences into account.

The pipe dream is that if you could just measure the weight of each syringe before and after adding insulin, you could get a more accurate microdose. I do have calipers and am familiar with that method, but I'm trying to see if there is a better, or just different, way to accurately measure microdoses. This weight idea might never work out (as 0.25 u of Lantus is 2.5 mg, a very small and very difficult amount to accurately measure), but maybe it will generate some other ideas on how to more accurately microdose.