HAC Water

HAC water is a diluent for reconstituting freeze-dried peptides, not an active compound. It consists of sterile water acidified with hydrochloric acid, plus glycerol and benzyl alcohol as preservative. The name is a trade designation; chemically it is a preserved, acidified water.

It exists for the few peptides that do not dissolve clearly in regular bacteriostatic water or fall back out of solution soon after. For anything that dissolves without trouble in bac water, which is most of the range, you do not need it. In the range it sits next to bac water and the 0.6% acetic acid, which does the same job with a different acid.

This information is for research and educational purposes only. No medical advice.

Three ingredients, three jobs. The hydrochloric acid lowers the pH. A peptide carries a different net charge at each pH. It is least soluble where that charge is close to zero. In acid, the carboxyl groups (aspartic acid, glutamic acid, C-terminus) lose their negative charge and histidine becomes positive as well. Together with the arginine and lysine side chains, which are positive anyway, the peptide turns net positive, the molecules repel each other and tend to stay apart rather than clump. The review by Zapadka and colleagues (2017) lists pH and net charge among the central levers for peptide aggregation.

Glycerol is a co-solvent. In work on proteins it keeps the structure more compact and lines water-repellent surface patches that would otherwise stick together (Vagenende et al., 2009). The composition does not state how much glycerol HAC water contains, so how strong this effect is in the vial cannot be put into numbers. Benzyl alcohol plays the same role as in bac water: it inhibits microbial growth and allows repeated withdrawals from a punctured vial.

There is a chemical side effect too: some peptide degradation routes, such as deamidation via a succinimide or reactions at disulfide bridges, run faster at neutral and basic pH than at mildly acidic pH. This is not a free pass, since strongly acidic solutions have degradation routes of their own, see the research section.

There are no studies on HAC water as a product, but there are on its three principles. The review by Nugrahadi and colleagues (2023) on peptides in aqueous solution concludes that the right pH and buffer are the most practical ways to stabilise a peptide, followed by co-solvents and polyols such as glycerol. Zapadka and colleagues (2017) describe how pH, net charge, concentration and excipients decide between amorphous aggregates and fibrils.

How strongly pH matters is shown by Hawe and colleagues (2009) with oxytocin: under heat it degraded fastest at pH 9, then at pH 7, then at pH 2 and slowest at pH 4.5. At pH 2 deamidation dominated, at pH 4.5, 7 and 9 oligosulfides and dimers formed. For oxytocin the most stable zone was therefore mildly acidic, while strong acid caused damage of its own. The best pH differs from peptide to peptide. The composition of HAC water does not state its pH. The comparable approved diluent in the next paragraph sits at pH 2, so there the acid is mainly a dissolving aid and no promise of a longer shelf life.

Glucagon shows that hydrochloric acid and glycerol are used as an approved diluent for a peptide: the US prescribing information of glucagon emergency kits lists water for injection with 12mg glycerin and 1mg hydrochloric acid per ml, pH 1.8 to 2.2, as the diluent. The glucagon powder is adjusted with hydrochloric acid to pH 2.5 to 3.0 during manufacture where needed. According to the same label, glucagon is barely soluble in water and only dissolves below pH 3 or above pH 9.5. For glycerol itself Vagenende and colleagues (2009) provide the mechanism. For benzyl alcohol the review by Meyer and colleagues (2007) shows it is, alongside phenol, the most common preservative in licensed peptide and protein products.

As a diluent HAC water has no effect of its own; the risks lie in handling and in compatibility with the peptide. Acidic solutions can sting more at the injection site than neutral ones, which is the most common practical difference from bac water. More diluent does not help, the pH stays practically the same and each dose then contains more acid. If you are sensitive, stay with peptides that do not need an acidic diluent.

• Not for every peptide: peptides that are stable in neutral water gain nothing from the acid. Strongly acidic pH brings degradation routes of its own (for oxytocin at pH 2 it was deamidation, Hawe et al. 2009). Use it only where there is a reason.
• Benzyl alcohol: occasionally skin reactions at the injection site. For newborns and infants benzyl alcohol is unsuitable as a matter of principle, which applies to every vial preserved with it.
• Lumps or precipitate: if particles or lumps remain even in HAC water, or the solution turns gel-like, it is not usable. Never inject particles. Slight cloudiness on its own is not a reason to discard it.
• Sterility: every withdrawal with a fresh sterile syringe, disinfect the septum first. The preservative does not replace clean technique.

Discard HAC water that is discoloured or open beyond the window. Store out of reach of children.

• Unopened: at room temperature, protected from light, until the printed expiry date. No fridge needed.
• Opened: 28 days from the first puncture, the usual window for preserved multi-dose vials. Write the date on the label.
• Reconstituted peptide: in the fridge at 2 to 8 °C, protected from light. As with bac water: usable for several months.

Do not freeze, neither the diluent nor the dissolved peptide. Keep the vial upright and hold it against the light before each withdrawal: clear and colourless is the normal state.

Unlike bac water, the cart does not add HAC water automatically, because only a few peptides need it. You add it to the cart yourself, as a 10-pack or as a single vial depending on what is on offer, with one 3ml vial for each peptide vial you want to dissolve with it.

You can remove the automatically added bac water in the cart if you use HAC water instead. If you keep both, you have the choice for every vial, which makes sense for the first attempt with a new peptide: bac water first, the acidic diluent only if the peptide does not dissolve in it.

Questions about the solubility of a specific peptide are answered by our support, just tell us product and size.