ZHICHENG BIO
Why “98% by HPLC” does not describe dihydromyricetin quality
DHM has two chiral centres, and the standard assay cannot see either of them. What to specify instead.
The short answer
Dihydromyricetin has two chiral centres, nature produces only the (2R,3R) form, and the achiral reversed-phase HPLC method behind every “98%” certificate in this trade cannot distinguish (2R,3R)-DHM from its enantiomer or from a racemic mixture. Optical purity is therefore an attribute that published work links to activity, that ordinary manufacturing conditions demonstrably put at risk, and that essentially no commercial specification states. Zhicheng Bio will report enantiomeric ratio by chiral HPLC or SFC together with specific optical rotation on the batch certificate for buyers who specify it.
- The molecule
- Dihydromyricetin (ampelopsin), CAS 27200-12-0, C15H12O8 — two chiral centres at C2 and C3; the natural configuration is (2R,3R)
- What the standard assay measures
- Content by achiral reversed-phase HPLC. Enantiomers are indistinguishable on an achiral column by construction — a racemate and a single enantiomer give the same 98%
- What published work shows
- After SFC separation, (−)-DHM was reported as more anti-inflammatory than both (+)-DHM and the racemate. The direction is counter-intuitive — the natural configuration is not uniformly the more active one — and it is reported here as published rather than as convenient
- Why configuration is at risk in manufacturing
- Racemisation accelerates markedly above 80 °C; Mg²⁺, Ca²⁺ and Mn²⁺ in process water promote it while Fe²⁺ inhibits it; pH below 5 protects and pH above 9 destroys (J Food Sci 2024)
- The uncomfortable overlap
- Published industrial routes use 90 °C hot-water extraction and cooling crystallisation that requires solvent above 85 °C and forbids rapid cooling — squarely inside the destructive window
- Regulatory gap
- No USP, EP, ChP or JP monograph exists for dihydromyricetin. China's 2026 Announcement No. 5 approved vine tea leaf polyphenols as a new food raw material at ≥85% polyphenols and ≤470 mg/day — a purely gravimetric specification with no stereochemical requirement at all
The measurement problem, stated precisely
A reversed-phase HPLC column separates compounds by polarity. Two enantiomers of the same molecule have identical polarity, identical UV spectra and identical mass. They are, to an achiral column, the same substance. This is not a limitation of any particular laboratory's method — it is a property of the technique.
So when a certificate of analysis reports “dihydromyricetin, 98.2% by HPLC”, the honest reading is: 98.2% of the material is dihydromyricetin in some stereochemical composition. A drum of pure (2R,3R)-DHM and a drum of fully racemised (±)-DHM both pass that test with the same number. Published work notes that some material sold as (+)-DHM is in fact racemic, which is the predictable consequence of specifying an attribute that the release method cannot see.
Resolving the enantiomers requires a chiral stationary phase — chiral HPLC or supercritical fluid chromatography — or, as a cheaper orthogonal check, a specific optical rotation measurement with the concentration, solvent, temperature and wavelength stated. Neither is exotic. Both are simply absent from the commercial norm.
Why the standard process is the thing that damages the attribute
The chiral instability of DHM has been quantified rather than merely asserted. Work published in Journal of Food Science in 2024 mapped four factors: temperature, with racemisation accelerating sharply above 80 °C and severely at 100 °C; water quality, with ultrapure water most stable and ordinary purified, mineral and tap water progressively worse; metal ions, where Fe²⁺ inhibits racemisation while Mg²⁺, Ca²⁺ and Mn²⁺ significantly promote it; and pH, protective below 5.0 and destructive above 9.0. Separate work in Food Chemistry the same year showed that thermal degradation in neutral water at 100 °C proceeds by five parallel routes — isomerisation, oxidation, hydroxylation, dimerisation and ring opening — rather than simply converting to myricetin.
Now lay those factors over the published manufacturing routes. Hot-water extraction at 90 °C. A cooling-crystallisation process that specifies solvent above 85 °C and warns explicitly that rapid cooling collapses yield — that is, a process rewarded for holding hot and cooling slowly. The official new-food-material route of ethanol extraction, decolourisation, concentration, filtration and drying. And ordinary process water carrying its own Mg²⁺ and Ca²⁺.
The overlap is close to total, and there is a perverse incentive inside it: because the release specification is achiral content, a process that holds material hot and cools it slowly scores well on the certificate while doing the most damage to the attribute the certificate does not measure.
What to write into a DHM specification
Ask for content by achiral HPLC, as now — that part of the industry norm is fine and necessary. Then add enantiomeric ratio or enantiomeric excess by chiral HPLC or SFC, with the column and conditions named, and specific optical rotation with concentration, solvent, temperature and wavelength stated. A reference standard is worth checking too: widely used commercial standards are themselves certified only to ≥98% by HPLC and carry no optical purity statement, so a chiral method validated against such a standard inherits an unstated assumption.
It is also worth agreeing process-side limits rather than only release-side ones, because this attribute is destroyed during manufacture and cannot be recovered by testing: a maximum process temperature, a water-quality requirement, and a pH ceiling. Those three lines do more for stereochemical quality than any tightening of the assay figure.
For pharmaceutical readers, none of this is novel: under ICH Q6A, enantiomeric purity is a routine specification item for a chiral single-enantiomer drug substance. The food and supplement ingredient trade is simply a step behind an already-settled norm on this point.
Where this leaves a buyer
If you are buying DHM as a commodity against a price per kilogram of “98%”, you are buying an attribute set that omits the one linked to activity, and you have no way to tell one supplier's drum from another's on that dimension. That is not an accusation against any particular supplier — it is a description of a specification norm that has not caught up with the published chemistry.
If you want the attribute, it has to be specified before the batch is made, named by method, and priced. Zhicheng Bio will report it on request; details of the grade and the second, ≥85% vine tea polyphenol grade are on the dihydromyricetin product page, and the purchasing questions are collected in the DHM purchasing guide.
Frequently asked
Does a 98% HPLC certificate prove DHM is the natural (2R,3R) form?
No. The assay behind that figure runs on an achiral reversed-phase column, and enantiomers are indistinguishable on an achiral column — identical polarity, identical UV, identical mass. Pure (2R,3R)-DHM and a fully racemised sample both return the same content figure. Proving configuration requires chiral HPLC or SFC, or a specific optical rotation measurement.
Why would DHM racemise during normal manufacturing?
Because the published racemisation conditions and the published extraction conditions overlap. Racemisation accelerates above 80 °C and is promoted by Mg²⁺, Ca²⁺ and Mn²⁺ in water and by pH above 9 (J Food Sci 2024), while standard routes use 90 °C hot-water extraction and cooling crystallisation held above 85 °C with deliberately slow cooling.
Is the natural (2R,3R) enantiomer the more active one?
Not according to the published comparison. After SFC separation, (−)-DHM was reported as more anti-inflammatory than both (+)-DHM and the racemate, and other work reports stronger antibacterial and antioxidant activity for (−)-DHM. This is reported here because it is what the literature says, not because it is commercially convenient. It does not establish a health effect of any product.
Is there a pharmacopoeial monograph for dihydromyricetin?
No monograph was found in USP, EP, ChP or JP. China's 2026 Announcement No. 5 approved vine tea (Nekemias grossedentata) leaf polyphenols as a new food raw material at ≥85% polyphenols with a limit of 470 mg per day, but that specification is gravimetric and sets no stereochemical requirement. In the absence of a monograph, the specification is whatever buyer and supplier agree in writing.
This page describes raw-material sourcing and specification. It is not a health claim and not medical advice. Last updated 2026-07-31.