| HS Code | 155008 |
| Product Name | 2,5-Diamino-4,6-dihydroxy pyrimidine hydrochloride Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable |
| Synonyms | 2,5-Diamino-4,6-dihydroxypyrimidine hydrochloride; 2,5-diaminopyrimidine-4,6-diol hydrochloride; 4,6-dihydroxy-2,5-diaminopyrimidine hydrochloride |
| Cas Number | 16018-83-2 (hydrochloride); free base: 551-20-6 |
| Molecular Formula | C4H7ClN4O2 |
| Molecular Weight | 178.58 g/mol |
| Iupac Name | 2,5-diaminopyrimidine-4,6-diol hydrochloride |
| Appearance | White to off-white crystalline powder |
| Assay | ≥98.0% (HPLC) |
| Grade | Pharma Grade / API Grade / GMP |
| Pharmacopoeia | USP/EP/BP/IP (as applicable) |
| Solubility | Soluble in water; slightly soluble in ethanol |
| Ph | 3.0-6.0 (1% aqueous solution) |
| Loss On Drying | ≤0.5% |
| Heavy Metals | ≤20 ppm |
| Residual Solvents | Meets ICH Q3C |
| Microbial Limits | Meets USP/EP |
| Endotoxin | ≤0.5 EU/mg (injectable grade) |
| Sterility | Sterile for injectable grade |
| Storage | Cool, dry, well-ventilated area; protected from light and moisture; injectable grade under sterile conditions |
| Shelf Life | 24-36 months when stored properly |
| Packaging | 1 kg, 5 kg, 25 kg fiber drums with double polyethylene bags; sterile packaging for injectable |
| Dosage Forms | Tablet, Capsule, Granule, Injection |
| Route Of Administration | Oral and Injectable |
| Hs Code | 2933.59 |
| Melting Point | >250°C (decomposes) |
As an accredited 2,5-Diamino-4,6-dihydroxy pyrimidine hydrochloride Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
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In direct-compression tablet manufacture, 2,5-diamino-4,6-dihydroxy pyrimidine hydrochloride is pre-screened through a 500 μm stainless-steel screen and dry pre-blended with microcrystalline cellulose, croscarmellose sodium, and colloidal silicon dioxide in a bin blender at 15–25 rpm for 10 min. Since the molecule carries two amino and two hydroxyl substituents on a pyrimidine ring, surface moisture can raise cohesion forces and promote sticking to punch faces; the processing suite is therefore held below 45% RH. A common direct-compression target for this compound is D10 ≥ 20 μm, D50 90–130 μm, and D90 ≤ 180 μm; a wider distribution increases the segregation risk in low-dose tablets and can produce weight variation outside PhEur 2.9.5 limits. Magnesium stearate is added at 0.25–0.75 wt% for 3–5 min; lubrication beyond 10 min reduces tensile strength, observed on production presses as capping and edge chipping at compaction forces below 8 kN. On a 16-station rotary press, the working compression range is 8–16 kN, and precompression force is set at 2–4 kN to evacuate air and reduce lamination. Ejection force is monitored at ≤500 N; higher values indicate insufficient lubricant dispersion or excess residual moisture. Content uniformity is verified by HPLC with stratified sampling; acceptance values follow USP <905>, and the assay result is calculated on an anhydrous basis after Karl Fischer water determination by USP <921>. Because published direct-compression data for this exact salt are limited, the stated values are conservative platform targets that require product-specific confirmation. Dissolution testing with USP <711> apparatus II at 50 rpm is product-specific; no compendial Q value applies to this active ingredient without a filed specification.
Capsule filling lines equipped with dosator nozzles impose tighter constraints on powder flow than tablet presses because the dosage chamber is filled by gravity and compression. For this compound, blends containing more than 0.5% acicular particles or fines below 20 μm can bridge inside the dosator tip, producing intermittent underfills; the practical remedy is to pre-blend with a small quantity of hydrophobic fumed silica or to pass the API through a pin mill at low speed. Powder bed height in the hopper is maintained at 60–80% of operating capacity because excessive head pressure densifies the bed and changes fill volume, while low bed height induces air entrainment. Fill weight acceptance for capsules is set at ±5% for individual units and ±3% for the mean, in line with USP <905> criteria scaled to the dosage unit mass. Because the salt is hygroscopic, hard gelatin capsules are preferred over cellulosic capsules when moisture sensitivity is documented; capsule shells are conditioned at 35–45% RH before filling, and equilibrium moisture content is kept below 14% for shell brittleness control. For low-dose strengths below 10 mg per capsule, a compatible diluent such as pregelatinized starch or lactose monohydrate is used at 70–90 wt% after confirming the absence of Maillard-type interactions with the primary amine groups. Blending is performed in a bin blender at 60–75% fill volume and 12–15 rpm for 15 min, with sampling at upper, middle, and lower ports to confirm blend uniformity before encapsulation. On production-scale dosator machines, tamping pin settings are adjusted so that the slug height is 1.5–2.5 mm below the capsule body rim; deviations outside this range are associated with split capsules and dust contamination.
For wet granulation trains handling this hydrochloride salt, the endpoint must be controlled by torque or power consumption rather than by a fixed water volume, because the amino and hydroxyl groups interact with water to create a cohesive mass that can shift rapidly from crumbly to over-wetted. The granulating liquid is purified water or a binder solution added at 8–15% w/w; if water alone is used, the liquid addition rate is limited to 0.2–0.5 kg/min per 100 kg powder load in a high-shear mixer to avoid local wet spots. Impeller tip speed is set between 4–8 m/s, and the chopper is operated at 1500–3000 rpm during the massing phase; sustained operation above 8 m/s raises product temperature beyond 35 °C and may accelerate oxidative discoloration of the pyrimidine ring. Wet massing time is 2–6 min after liquid addition; longer massing increases granule density and reduces porosity, which can delay disintegration. The wet granules are transferred to a fluid-bed dryer with inlet air dew point below 5 °C and inlet air temperature set at 60–70 °C; product temperature is held at 38–42 °C until loss on drying falls to 1.5–2.5%. Dried granules are milled through a 1.0 mm rasp screen at 1000–1500 rpm; milled granule size distribution is targeted at D10 ≥ 45 μm, D50 180–350 μm, and D90 ≤ 850 μm to ensure acceptable flow and compression. Tablet hardness after compression from these granules is typically in the range 60–120 N, but the criterion is not fixed without product-specific data. The final granulation is blended with crospovidone and sodium stearyl fumarate for 5–10 min, and the mass is compressed within 24 h to limit moisture re-uptake.
Aqueous injectable solutions prepared from the hydrochloride salt are processed under dissolved-oxygen control because the pyrimidine ring is susceptible to oxidative degradation in the presence of trace transition metals. Nitrogen sparging through 0.22 μm filters is used to reduce headspace oxygen below 2% before and after filling. The formulation pH is maintained with a suitable buffer at a value selected from stability data; because the salt contains weakly basic amino groups and acidic hydroxyl groups, pH shifts during terminal sterilization can alter the ionization state and may cause precipitation or color development. Terminal sterilization by saturated steam is performed at 121 °C for 15 min when solution stability data permit; the F0 value is calculated according to PhEur 5.1.1 and should be not less than 8 min for routine moist-heat sterilization of aqueous products. If pH drift after sterilization exceeds 0.3 pH units, buffer capacity is insufficient for that formulation. Solutions are filtered through 0.22 μm PVDF or PES membranes; membrane filter compatibility is verified by extractable testing under simulated production conditions. Particulate matter is controlled to USP <788> limits. Bacterial endotoxin testing by USP <85> or PhEur 2.6.14 is applied to final filled units; the limit is assigned based on the maximum daily dose. Sterile filtration and aseptic filling are required for formulations that cannot tolerate terminal steam sterilization; in that case, filter integrity is tested by bubble point or diffusion flow before and after filling.
Oral granule and single-dose sachet filling require the API to be incorporated into free-flowing granules rather than powders, because dusting from low-density powder blends creates fill weight variation and cross-contamination on vertical form-fill-seal machines. The salt is pre-blended with a carrier such as sorbitol or maltodextrin and a low-substituted cellulose disintegrant; the pre-mix is then wet-granulated or dry-compacted to produce granules with a bulk density of 0.55–0.75 g/mL. Granule flow through filling tubes is checked by the standard funnel method; a flow rate below 10 g/s through a 15 mm orifice indicates the need for additional glidant or a second milling pass. Sachet fill weight targets are set with acceptance limits of ±5% for individual sachets and ±2% for the batch mean; equipment with auger fillers is preferred over cup fillers when granule density is not uniform. The granules are dried to a moisture content of 1.0–2.0% before filling to limit sticking on the heat-sealing jaws; sealing temperature is set at 140–160 °C for polyethylene terephthalate/aluminium/low-density polyethylene laminates. Dissolution of granules for oral administration is evaluated after reconstitution in water at 25 °C and 37 °C; if the granulated product is intended as an oral suspension, sedimentation volume and redispersibility are also measured. The presence of the hydrochloride salt may lower the pH of the reconstituted suspension; therefore the formulation is adjusted with a pharmaceutically acceptable acid or base as required and the pH value is reported by USP <791>.
When the hydrochloride salt is formulated into a lyophilized injectable, the critical process parameters shift from thermal sterilization to freezing rate, primary drying chamber pressure, and collapse temperature. The solution is filled into vials after sterile filtration at 2–8 °C; the fill volume is determined by the target dose and by the cake height, which should remain below 70% of the vial body height to avoid ejection of solids from the neck during freeze-drying. Freezing is performed on a shelf at −40 °C for at least 2 h; formulations with bulking agents such as mannitol or trehalose at 3–8 wt% reduce cake collapse and improve plug appearance. Primary drying is conducted at a chamber pressure of 0.1–0.2 mbar and shelf temperature ramped from −30 °C to 20 °C over 24–48 h; the ramp rate is not more than 0.5 °C/min to avoid microcollapse. Secondary drying at 30–40 °C for 6–12 h reduces residual moisture below 1.0%; higher moisture in the plug shortens the reconstituted solution stability. Cake appearance is inspected for uniform color and absence of shrinkage; lyophilized cakes that are cracked or detached from the vial wall are rejected as part of visual inspection. Reconstitution time with water for injection at 25 °C should not exceed 2 min with gentle swirling; undissolved particles indicate incomplete primary drying or precipitation due to pH shifts during freezing.
| Attribute | Method | Release criterion |
|---|---|---|
| Assay | HPLC, ICH Q2(R1) | 95.0–105.0% of labelled amount |
| Residual moisture | USP <921> Karl Fischer | ≤ 1.0% w/w in lyophilized plug |
| Reconstitution time | Visual, with WFI at 25 °C | ≤ 2 min |
| pH after reconstitution | USP <791> | Product-specific range, typically ± 0.5 pH unit from target |
| Particulate matter | USP <788> | ≤ 6000 particles per container at ≥10 μm; ≤600 particles per container at ≥25 μm for small-volume injections ≤100 mL |
| Bacterial endotoxins | USP <85> | Not more than assigned limit based on dose |
| Sterility | USP <71> | No growth |
Bulk API handling and packaging for oral and injectable supply chains are constrained by the salt’s moisture sensitivity and electrostatic charging. The dispensed API is double polyethylene-lined and sealed under nitrogen when the equilibrium relative humidity in the warehouse exceeds 60%; silica gel desiccant is inserted at 5–10 g per 25 kg drum, and the drum closure torque is verified to 25–35 N·m. Micronization and sieving are conducted in a nitrogen-purged isolator to reduce occupational exposure and oxidative dust formation; the process air dew point is held below −20 °C. Bulk hold time studies are performed under ICH Q1A(R2) climatic zones I and II conditions with testing at 0, 3, 6, 9, and 12 months; samples are stored at 25 °C/60% RH and 30 °C/65% RH. The hydrochloride salt is assigned a retest period based on quantified organic impurities; if a specified impurity exceeds the qualification threshold defined under ICH Q3A(R2), the lot is not released. Cleaning validation on downstream packaging lines uses swab and rinse sampling with acceptance limits calculated from health-based exposure data under ICH Q3D; residual API in rinse water is determined by HPLC at a detection limit below 10 ppm. For export cartons, desiccated and oxygen-barrier packaging is required when the API is shipped through tropical climates; container closure integrity is tested by dye penetration per USP <1207> or vacuum decay.
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Model designation: 2,5-Diamino-4,6-dihydroxy pyrimidine hydrochloride, Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable. The hydrochloride salt is supplied as a crystalline powder with the molecular formula C₄H₇ClN₄O₂ and a relative molecular mass of 178.58, compared with 142.12 for the free base. The stoichiometric chloride content is 19.86%. The material is manufactured under cGMP as defined in 21 CFR 210 and 21 CFR 211, with active pharmaceutical ingredient quality-system controls consistent with ICH Q7. The product model distinguishes oral solid grades and injectable grades by particle-size distribution, water content, microbial quality, and endotoxin burden. For tablet and capsule operations, the API is controlled for powder flow, compressibility, and blend uniformity; for granule-based processes, wet and dry granulation endpoints are influenced by the hydrochloride counterion and residual water. For injection, the product is controlled for pyrogens by Ph. Eur. 2.6.14 and for subvisible particulate matter by Ph. Eur. 2.9.19. The therapeutic indication is outside the scope of this technical description.
In solid oral processing, the hydrochloride salt is evaluated for particle-size distribution using laser diffraction according to ISO 13320-1:2020. The D90 is commonly controlled below 75 µm for dry blending and below 250 µm for wet granulation when a preliminary sieving step is used; these ranges are process-dependent and should be confirmed against the manufacturer’s certificate of analysis. Moisture content is determined by Ph. Eur. 2.5.12 or USP <921> method Ia, with an oral-grade upper limit typically set at 0.5% to reduce agglomeration and weight variation. In direct compression, flowability is measured by Ph. Eur. 2.9.36 or USP <1174> and is affected by crystal habit; where the D90 falls below 75 µm without suitable wetting, flow control may require pre-blending with a glidant. Blend uniformity is verified by stratified sampling following USP <905> or Ph. Eur. 2.9.40. Capsule filling imposes similar particle-size controls, but tamping and dosator filling can increase sensitivity to powder adhesion on stainless-steel contact surfaces. Granule processes use the hydrochloride salt in aqueous binder solutions; the chloride counterion depresses granulating-fluid pH and can alter binder hydration. A pilot-scale high-shear granulator with a 10 L bowl and impeller tip speed of 2–5 m/s is used to establish endpoint by torque and mass rheology, but published data for this specific API are limited.
For tablet and capsule formulations containing 2,5-diamino-4,6-dihydroxy pyrimidine hydrochloride, tabletability is assessed with a compaction simulator or single-station press. Preformulation screens should include compatibility studies with microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and pregelatinized starch; binary mixtures are stored at 40 °C/75% RH in open containers for 4 weeks to detect hydrochloride-mediated degradation or color change. The API is sensitive to alkaline granulating fluids; formulations containing carbonate salts or dibasic sodium phosphate may produce free-base precipitation and should be evaluated by slurry pH monitoring. Aqueous film coating of tablets can proceed after core preheating to below 45 °C bed temperature to limit moisture uptake; tablet cores containing the hydrochloride salt should be stored in HDPE containers with desiccant if the equilibrium moisture content exceeds 2.0%. Dissolution testing is conducted with USP <711> apparatus 2 at 50 rpm in 900 mL of dissolution medium; medium selection must consider the salt’s pH-dependent solubility and not exceed pH 6.8 unless the formulation is intended for enteric release.
Direct compression of the hydrochloride salt becomes process-critical when the D90 is below 75 µm and the powder exhibits low bulk density. At this particle-size threshold, flow through a rotary tablet press feed frame may become irregular, leading to weight variation exceeding 2.0% RSD in commercial batches. In such cases, dry granulation by roller compaction is specified with a roll gap of 1.0–2.5 mm and a compaction force selected to achieve ribbon solid fraction between 0.55 and 0.75; these values are typical for pharmaceutical powders and are not a substitute for product-specific development data. The granulate is milled through a 0.8 mm screen and blended with lubricants at low shear. If wet granulation is preferred, the granulating fluid is acidified with dilute hydrochloric acid to maintain the salt form and reduce the risk of free-base precipitation; granulation endpoint is monitored by impeller torque and not by time alone. The granules are dried in a fluid-bed dryer with inlet air temperature not exceeding 60 °C to a final moisture content of 0.5–1.5%, then lubricated and compressed. Process analytical technology may be applied by near-infrared spectroscopy for moisture and blend uniformity, with calibration models validated according to ICH Q2(R1).
The hydrochloride salt differs from the free base in aqueous solubility, hygroscopicity, and pH of the saturated solution. The free base is less water-soluble because the hydroxyl groups at positions 4 and 6 remain largely unionized and the heterocyclic nitrogen atoms form intramolecular hydrogen bonds; the hydrochloride salt disrupts this network by protonation of the amino group and chloride counterion association. The theoretical chloride content of 19.86% provides a direct quality control marker by argentometric titration according to Ph. Eur. 2.5.4. Compared with sulfate salts, the hydrochloride form generally exhibits lower residue on ignition, lower molecular mass per active moiety, and a simpler counterion with no risk of sulfate-induced incompatibility in calcium-containing parenteral fluids. Published comparative solubility data for this exact pyrimidine system are limited; therefore, salt selection should be confirmed by shake-flask solubility in biorelevant media at 37 °C and pH values of 1.2, 4.5, and 6.8. The hydrochloride form is preferred when the final dosage form requires a chloride-containing tonicity agent such as sodium chloride, because no additional counterion is introduced. In tablet film-coating systems, the chloride salt may accelerate corrosion of uncoated tool steel, so contact surfaces are specified with 316L stainless steel or hard-chrome plating.
| Control parameter | Oral solid grade method / limit | Injectable grade method / limit |
|---|---|---|
| Identification | IR and HPLC retention time; Ph. Eur. 2.2.24 | IR and HPLC retention time; Ph. Eur. 2.2.24 |
| Assay on dried basis | 98.0%–102.0%; HPLC Ph. Eur. 2.2.29 | 98.0%–102.0%; HPLC Ph. Eur. 2.2.29 |
| Water content | NMT 0.5%; Ph. Eur. 2.5.12 | NMT 0.2%; Ph. Eur. 2.5.12 |
| Chloride content | 19.0%–20.5%; Ph. Eur. 2.5.4 | 19.0%–20.5%; Ph. Eur. 2.5.4 |
| Residue on ignition | NMT 0.1%; Ph. Eur. 2.4.16 | NMT 0.1%; Ph. Eur. 2.4.16 |
| Related substances | Unspecified impurity NMT 0.10%; total NMT 1.0%; ICH Q3A | Unspecified impurity NMT 0.10%; total NMT 1.0%; ICH Q3A |
| Endotoxin | Not applicable unless used in oral liquid | Derived from maximum dose; Ph. Eur. 2.6.14 |
| Subvisible particulate matter | Not applicable | Ph. Eur. 2.9.19; USP <788> |
| Elemental impurities | ICH Q3D risk assessment | ICH Q3D risk assessment |
Injectable processing of 2,5-diamino-4,6-dihydroxy pyrimidine hydrochloride requires a dedicated line with stainless-steel contact surfaces of 316L or higher, because the chloride counterion in aqueous solution can initiate pitting corrosion on lower grades. The bulk solution is prepared in water for injection at 15–25 °C, with pH adjusted using dilute hydrochloric acid or sodium hydroxide; the pH target is formulation-dependent and must be selected by forced degradation studies. Terminal sterilization by moist heat at 121 °C for 15 minutes is evaluated for hydrolytic degradation; if the active moiety shows more than 0.2% new impurity formation, aseptic filtration through 0.22 µm polyethersulfone filters is used. For lyophilized products, the solution is filled into Type I borosilicate glass vials and lyophilized with primary drying shelf temperature not exceeding −25 °C to maintain cake structure; published data for this specific API are limited and cycle parameters must be developed with product-specific thermal characterization. The freeze-dried cake is reconstituted with sterile water for injection to a target concentration of 10 mg/mL; osmolality is adjusted with sodium chloride to 270–330 mOsm/kg. The final injectable product is tested for sterility by Ph. Eur. 2.6.1 and bacterial endotoxins by Ph. Eur. 2.6.14.
The hydrochloride salt interacts with excipients through acid-base and chloride-mediated mechanisms. In tablet matrices containing magnesium stearate, the chloride salt can increase free fatty acid release at high humidity, leading to soft tablet cores. Mixtures with crospovidone may retain water and shift the local pH at the particle surface; this is measured by slurry pH and near-infrared chemical imaging. The salt is incompatible with strong alkalizing agents such as meglumine or tromethamine in injectable formulations because free base precipitation occurs above pH 5.5. Compatibility with antioxidants in parenteral products requires forced degradation at 40 °C for 14 days in the presence of oxygen; sulfite-based antioxidants may reduce assay recovery and should be avoided unless demonstrated to be compatible by HPLC peak purity. The chloride content also influences conductivity during lyophilization, which affects ice nucleation and primary drying resistance. These interactions are specific to the hydrochloride form and are not extrapolatable to the free base or mesylate salts.
The API is characterized by reversed-phase HPLC with a C18 column of 150 mm × 4.6 mm, 5 µm particle size, using a mobile phase of phosphate buffer and acetonitrile. Detection is by UV at 254 nm; the method is validated for specificity, linearity, accuracy, precision, and robustness according to ICH Q2(R1). The hydrochloride salt gives a distinct chloride peak in ion chromatography, which is used to confirm counterion stoichiometry. Potential impurities include the free base and position isomers; their resolution is confirmed by system suitability with a resolution factor of not less than 2.0 between critical pairs. For injectable applications, the method should be capable of detecting polar degradants formed by hydrolysis at pH extremes; forced degradation under acidic, alkaline, oxidative, thermal, and photolytic conditions is conducted according to ICH Q1A(R2) and ICH Q1B. The limit of quantitation for unspecified impurities is typically 0.05%, and the reporting threshold follows ICH Q3A for active substances. Residual solvents are controlled by headspace gas chromatography according to Ph. Eur. 2.4.24, with limits assigned to Class 1, Class 2, and Class 3 solvents under ICH Q3C. The material is screened for elemental impurities by ICP-MS after closed-vessel digestion, as required by ICH Q3D.
The hydrochloride counterion provides a balance of aqueous solubility, crystallinity, and compatibility with chloride-based diluents. Compared with the free base, the hydrochloride salt lowers the pH of the saturated solution and shifts dissolution from the surface-controlled to diffusion-controlled regime in acidic media. This difference is measured by intrinsic dissolution rate under sink conditions with a rotating disk apparatus at 100 rpm and 37 °C; published intrinsic dissolution values for this specific configuration are limited. The free base may require micronization to achieve similar dissolution performance, which introduces opportunities for agglomeration and electrostatic charging. Sulfate or besylate salts introduce additional mass and may contribute to higher residue on ignition, which is undesirable for injectable products with stringent particulate requirements. The chloride salt is also compatible with parenteral sodium chloride tonicity adjustment, avoiding counterion exchange in the finished product. For oral granules, the hydrochloride salt can be coated with amino methacrylate copolymers to provide modified release; chloride ions do not interfere with enteric polymer dissolution at pH 6.8. The main limitation is hygroscopicity above 60% RH; open handling should be restricted to 40% RH or lower, and bulk packaging should include desiccant and polyethylene liners.
In manufacturing facilities where ambient relative humidity exceeds 60%, wet granulation of the hydrochloride salt can produce granules with residual moisture above 2.0% after drying. This condition increases tablet hardness variability and causes picking or sticking during compression. The drying step is therefore controlled by measuring outlet air dew point and granule moisture using loss on drying at 105 °C for 5 minutes or by near-infrared spectroscopy. Fluid-bed drying is preferred over tray drying because of shorter exposure time at elevated temperature; inlet air temperature is maintained at 50–60 °C. If the granule moisture remains above 1.5%, tablet compression should be halted and the material re-dried to avoid punch filming. The chloride salt may also cause corrosion on aluminum drying trays; trays should be constructed of 316L stainless steel or coated with a polymer lining. These operational boundaries are based on pharmaceutical manufacturing practice for hygroscopic hydrochloride APIs and should be confirmed by site-specific process qualification.
Bulk packaging for 2,5-diamino-4,6-dihydroxy pyrimidine hydrochloride comprises double polyethylene bags sealed with desiccant inside an HDPE drum. The recommended storage condition is 2–8 °C for the injectable grade and ≤25 °C for the oral solid grade, protected from moisture and light. Re-test interval is established by long-term stability data under ICH Q1A(R2); typical re-test period is 24 months for the oral solid grade when stored at 25 °C / 60% RH, while the injectable grade may require 12 months at 5 °C. These values are product-specific and should be confirmed with the manufacturer. Each batch is released with a certificate of analysis reporting assay, water content, chloride content, related substances, residual solvents, elemental impurities, and microbial limits where applicable. The product is not approved as a sterile API; terminal sterilization or aseptic filtration must be performed during finished product manufacture.
Unlike 2,4-diamino-6-hydroxy pyrimidine, the 2,5-diamino-4,6-dihydroxy substitution pattern places amino groups at positions 2 and 5 and hydroxyl groups at positions 4 and 6; this arrangement alters hydrogen-bonding capacity and may influence crystal packing. The hydrochloride salt of the 2,5-isomer is more polar than the corresponding 2,4-isomer and may exhibit different retention behavior on reversed-phase HPLC. The distinction is critical in manufacturing because the position isomers can co-synthesize; the specification limits the isomeric impurity to NMT 0.10% by HPLC. Compared with 2,4-diamino-6-hydroxy pyrimidine hydrochloride, the 2,5-diamino-4,6-dihydroxy pyrimidine hydrochloride has two hydroxyl groups and two amino groups, yielding a higher chloride stoichiometry per molecule and different pH-dependent solubility. No inference about pharmacological equivalence between these isomers should be made from this technical distinction.
