Source of Reconstitution calculator

{{Infobox tool | name = Reconstitution calculator | subtitle = Interactive reference tool | image = syringe.svg | caption = A U-100 syringe scale is a volume scale: 42 units is 0.42 mL regardless of what the vial contains. | Inputs = Vial mass (mg), diluent volume (mL), dose (mg or µg), syringe scale | Outputs = Concentration, dose volume, syringe units, doses per vial <!-- Method --> | Concentration = {{math|C = m / V}} | Dose volume = {{math|V_{d} = D / C}} | Syringe units = {{math|U = V_{d} × S}}, S = 100, 50 or 40 per mL | Assumption = Negligible volume displacement by the solid <!-- Scope --> | What it is = A unit converter | What it is not = A clinical decision tool | Runs = Entirely in the browser }} {{hatnote|For the underlying procedure and its sources, see [[Reconstitution of lyophilised peptides]]. For the syringe scales, see [[Insulin syringe unit conversion]].}} The '''reconstitution calculator''' relates the four quantities involved in dissolving a lyophilised peptide and drawing a dose from it: the mass of solid in the vial, the volume of diluent added, the intended dose, and the reading on the syringe barrel. All four are connected by one division, and almost every error reported in the literature and in community accounts is a confusion between two of them rather than a failure of the arithmetic itself.{{r|usp797}} The calculation is a [[Project:No original research|routine unit conversion]]: concentration is mass divided by volume, dose volume is dose divided by concentration, and a syringe unit is one hundredth of a millilitre on the U-100 scale. The tool below performs those operations and shows each intermediate result, because the intermediate is where a mistake becomes visible. This page is a reference tool and '''not a clinical decision aid'''. It converts numbers a reader enters; it does not select a dose, and it has no knowledge of the vial, the label claim, or the person. See [[Project:Medical disclaimer]]. == The calculator == Enter the label mass of the vial, the volume of diluent, and the intended dose. The tool reports the resulting concentration, the volume that dose occupies, the reading on the selected syringe scale, and how many doses the vial contains. == Worked examples == The tool's defaults correspond to the first row below. Each row is a division; none of them requires a calculator, and reproducing one by hand is a useful check that the inputs were entered as intended. |+ Concentration and dose volume for common vial and diluent combinations | Vial | Diluent | Concentration | Dose | Dose volume | U-100 units | |---|---|---|---|---|---| | 5 mg | 2.0 mL | 2.5 mg/mL | 0.25 mg | 0.10 mL | 10 | | 5 mg | 2.0 mL | 2.5 mg/mL | 0.50 mg | 0.20 mL | 20 | | 5 mg | 1.0 mL | 5.0 mg/mL | 0.25 mg | 0.05 mL | 5 | | 10 mg | 2.0 mL | 5.0 mg/mL | 2.5 mg | 0.50 mL | 50 | | 10 mg | 1.0 mL | 10 mg/mL | 1.0 mg | 0.10 mL | 10 | | 15 mg | 3.0 mL | 5.0 mg/mL | 7.5 mg | 1.50 mL | 150 | | 2 mg | 2.0 mL | 1.0 mg/mL | 100 µg | 0.10 mL | 10 | The last row illustrates the most common unit confusion: a dose expressed in micrograms against a concentration expressed in milligrams per millilitre. One thousand micrograms is one milligram, so 100 µg of a 1 mg/mL solution is 0.1 mL — ten units on a U-100 syringe, not one hundred. Two rows are worth noticing for a different reason. A 150-unit dose does not fit in a 1 mL insulin syringe, and the tool warns when a computed volume exceeds a plausible barrel. A 5-unit dose sits at the very bottom of a U-100 barrel, where the graduation interval is a large fraction of the dose and precision is correspondingly poor; a lower concentration would place the same dose further up the scale.{{r|iso7886}} == What the label mass means == {{main|Peptide content}} The calculation above treats the vial's label mass as the mass of peptide present. That is an assumption, and on a [[Certificate of analysis|certificate of analysis]] it is frequently not true. A lyophilised solid contains water ([[Karl Fischer titration|typically 3–8% by mass]]), a [[Trifluoroacetate counterion|counterion]] (2–12%), and residual salts, all of which occupy the labelled mass unless the label claim is explicitly a net peptide figure.{{r|usp1503}} A vial labelled 10 mg with 5.2% water and 6.4% trifluoroacetate contains approximately {{math|10 × (1 − 0.052 − 0.064) ≈ 8.7\,mg}} of peptide-plus-related-substances, before any correction for chromatographic purity. Entering 10 mg into the calculator therefore yields a concentration about 13% higher than the peptide concentration actually achieved. {{note|Whether that discrepancy constitutes [[Underfilling|underfilling]] depends on whether the label claim is a gross fill weight or a net peptide claim — a distinction certificates commonly leave implicit. PeptidePedia Wiki treats it as unresolved unless the supplier states which it is.}} == Volume displacement and dead space == Two systematic effects are worth stating because the calculator does not model the first and only optionally models the second. '''Displacement.''' Adding 2 mL of diluent to a vial containing 5 mg of solid produces slightly more than 2 mL of solution, because the dissolved solid occupies volume. For peptide masses of a few milligrams in a millilitre or more of diluent the effect is on the order of a few thousandths of a millilitre and is negligible against the graduation interval of the syringe. It ceases to be negligible when the solid mass approaches the diluent volume, which does not arise in the cases this tool is used for. '''Dead space.''' Volume retained in the syringe hub and needle after the plunger is fully depressed is not delivered. Reported figures range from roughly 0.02 mL for a low-dead-space insulin syringe with a fixed needle to 0.07 mL or more for a detachable-needle arrangement.{{r|whodeadspace}} Against a 0.10 mL dose that is a 20–70% loss if the syringe is not primed, which is why the dead-space field exists: entering a figure shows its effect on the number of doses the vial yields, not on the delivered dose, since a primed syringe delivers its nominal volume. {{figure|syringe|Graduations on a 1 mL U-100 barrel. The scale reads volume; the mass it corresponds to depends entirely on the concentration in the vial.}} == Limitations == The tool assumes complete dissolution, an accurate label mass, an accurately measured diluent volume, and a syringe manufactured to its nominal scale. Each of those is an approximation: * incomplete dissolution leaves a concentration lower than calculated and a suspension of unknown uniformity; * diluent volume drawn on the same syringe used for dosing carries that syringe's own error; * syringe volume tolerance under ISO 7886 is a few percent of nominal capacity, which at the bottom of the barrel is a large fraction of a small dose;{{r|iso7886}} * [[Peptide aggregation|aggregated]] or partly degraded material has a peptide content lower than the certificate reports, and no arithmetic detects that. It performs no clinical reasoning of any kind. It does not know what compound is in the vial, whether the compound is approved for human use, or whether the entered dose has ever been studied. Compounds distributed for research are '''not approved for human use''' in any major jurisdiction. == References == {{reflist}} <ref name="usp797">United States Pharmacopeia, General Chapter <797>, "Pharmaceutical Compounding — Sterile Preparations". USP–NF, current revision.</ref> <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, "Quality Attributes of Synthetic Peptide Drug Substances" (informational). USP–NF, current revision.</ref> <ref name="iso7886">ISO 7886-1, ''Sterile hypodermic syringes for single use — Part 1: Syringes for manual use''. International Organization for Standardization.</ref> <ref name="whodeadspace">World Health Organization, ''WHO Guideline on the Use of Safety-Engineered Syringes'' (2015) — includes dead-space characterisation of syringe types.</ref> == Further reading == * International Council for Harmonisation, ''Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products''. == See also == * [[Reconstitution of lyophilised peptides]] * [[Insulin syringe unit conversion]] * [[Bacteriostatic water]] * [[Syringe dead space]] * [[Peptide content]] * [[Karl Fischer titration]] {{DEFAULTSORT:Reconstitution calculator}} [[Category:Interactive reference tools]] [[Category:Unit conversion]] [[Category:Preparation and handling]] [[Category:Dosing and titration]]