| HS Code | 976329 |
| Product Name | 4-Dimethylaminophenol Veterinary Grade API |
| Chemical Name | 4-(Dimethylamino)phenol |
| Cas Number | 619-60-3 |
| Molecular Formula | C8H11NO |
| Molecular Weight | 137.18 g/mol |
| Appearance | White to off-white crystalline powder |
| Solubility | Soluble in water, ethanol, and chloroform; slightly soluble in ether |
| Melting Point | 75 to 77 °C |
| Loss On Drying | NMT 0.5% |
| Sulfated Ash | NMT 0.1% |
| Heavy Metals | NMT 10 ppm |
| Assay | NLT 98.0% on dried basis |
| Pharmacological Category | Methemoglobin-forming antidote |
| Veterinary Indication | Antidote for cyanide poisoning in veterinary practice |
| Dosage Form Compatibility | Compatible with tablets, injections, capsules, powders, granules, premix, and solutions |
| Storage Conditions | Store in tightly closed, light-resistant containers in a cool, dry place; protect from moisture |
As an accredited 4-Dimethylaminophenol Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 4-Dimethylaminophenol Veterinary Grade API packed in sealed 25 kg drums with tamper-evident closure and inert liner, labeled for pharmaceutical use. |
| Container Loading (20′ FCL) | One 20′ FCL contains palletized, secured drums of 4-Dimethylaminophenol veterinary-grade API, safely packed for tablets, injections, capsules, powders, granules, premix, and solutions. |
| Shipping | Shipping is conducted in sealed, light-resistant containers to prevent degradation. Product must be kept dry, cool, and away from ignition sources. Shipments comply with hazardous material regulations, with clear labeling and documentation for veterinary use. Proper handling and temperature control ensure stability during transit for downstream pharmaceutical formulation. |
| Storage | Store 4-Dimethylaminophenol Veterinary Grade API in tightly sealed, light-resistant containers, protected from moisture and air. Keep in a cool, dry, well-ventilated area away from oxidizers and incompatible materials. Maintain moderate temperatures, avoid prolonged heat, and ensure containers remain closed when not in use to preserve stability and potency. |
| Shelf Life | 4-Dimethylaminophenol veterinary grade API has a shelf life of 24 months when stored unopened in a cool, dry, light-protected area. |
A sterile aqueous parenteral dosage form for 4-dimethylaminophenol is engineered around the compound’s susceptibility to oxidative colour shift and its narrow stable pH window of 3.5–4.5. Formulation batch records specify an active charge of 50.0 g/L as base equivalent, equivalent to 5.0% w/v, with a correction factor of 1.266 when the hydrochloride salt is dispensed. Compounding takes place in 316L stainless-steel vessels under nitrogen overlay using Water for Injection cooled to 20–25°C; oxygen enters through silicone transfer lines if low-permeability EPDM or equivalent gasketed tubing is not substituted, and deviation investigations have linked headspace oxygen above 2.0% v/v to visible pink-to-brown discolouration within 48 h. The solution is adjusted to pH 4.0 ± 0.2 with 0.1 N hydrochloric acid, filtered through a 0.22 µm polyethersulfone membrane at a differential pressure not exceeding 0.5 bar, and filled into amber Type I glass vials closed with bromobutyl rubber stoppers under nitrogen-flushed headspace. Sterility assurance follows USP <71>, endotoxin control follows USP <85> with an acceptance limit of <0.5 EU/mL, particulate matter is controlled by USP <788>, and finished release complies with 21 CFR 211.165 and EU Regulation (EU) 2019/6 for veterinary medicinal products. The terminal finished product type is a ready-to-administer injectable solution for intravenous use in adult cattle and sheep exposed to cyanogenic forage.
When a field supply chain cannot maintain 2–8°C beyond 72 h, the product is lyophilized into a sterile powder for reconstitution rather than distributed as a ready-to-use solution. A typical vial contains 500 mg of 4-dimethylaminophenol base equivalent with 40 mg/mL mannitol as a crystalline bulking agent and a 10 mM citrate buffer adjusted to pH 4.0 ± 0.2. The freeze-drying cycle uses a shelf ramp of 0.5°C/min to -40°C, an annealing step at -10°C for 2 h, primary drying at -20°C and 0.2 mbar for 36 h, and secondary drying at 25°C for 8 h; thermocouple data from 12 m² production units show edge vials reaching target moisture faster than centre vials, requiring cyclic air circulation balancing to prevent cake collapse. Residual moisture is measured by USP <921> Karl Fischer titration with a release limit of <1.0% w/w, and water activity by USP <922> remains <0.3 aw to inhibit hydrolytic degradation. The container closure system consists of 10 mL glass vials sealed with fluoropolymer-coated bromobutyl stoppers, and the final product type is a sterile lyophilized powder for injection, reconstituted to 10 mL with Water for Injection to yield 50 mg/mL immediately before intravenous administration.
Oral drench solutions for pre-ruminant calves and lambs require a different formulation architecture because the product is not terminally sterilized and may remain in partially opened bottles for 7–14 days under farm storage. The active is incorporated at 10 mg/mL as base equivalent, with 0.1% w/v sodium metabisulphite as antioxidant and 0.01% w/v disodium edetate as metal-ion chelator, in a citrate buffer at pH 4.0 ± 0.3. Manufacturing uses a 500 L stainless-steel vessel with low-shear impeller at 300 rpm, nitrogen sparging through a 0.45 µm sintered filter, and sequential addition of the active under vacuum transfer to minimize powder aeration. The solution is filled into 250 mL amber polyethylene terephthalate bottles with induction-sealed aluminium-lined caps, and microbiological quality follows Ph. Eur. 5.1.4 acceptance criteria for non-sterile oral liquids. The finished product type is an oral drench solution for neonatal ruminants without established rumen detoxification capacity.
| Dosage form | Critical quality attribute | Test method | Acceptance limit |
|---|---|---|---|
| Ready-to-use injectable solution | Visible particulates | USP <788> | Meets light obscuration method for ≥10 µm and ≥25 µm |
| Lyophilized powder for injection | Residual moisture | USP <921> Karl Fischer | <1.0% w/w |
| Oral drench solution | Non-sterile microbial limits | Ph. Eur. 5.1.4 | Total aerobic count ≤10² CFU/g |
| Rapid-disintegration tablet | Disintegration time | USP <701> | <30 min |
| Powder/granule premix | Blend uniformity | Ph. Eur. 2.9.40 | Acceptance value ≤15 |
Because tablet compression generates localized thermal and shear stress, the formulation is designed to minimize amorphous transition and discolouration. A direct-compression core consists of 32.5 mg 4-dimethylaminophenol base equivalent per 200 mg tablet, corresponding to 16.25% w/w, with microcrystalline cellulose at 68.75% w/w, croscarmellose sodium at 3.0% w/w, colloidal silicon dioxide at 0.5% w/w, and magnesium stearate at 0.5% w/w. If ambient relative humidity exceeds 60%, the active is pre-dried at 40°C for 2 h before blending. Blending is performed in a 300 L V-blender at 15 rpm for 10 min before lubricant addition and a final 3 min blend; target compression force on a 16-station rotary press is 8–12 kN, producing tablet hardness of 40–70 N. Disintegration is tested by USP <701> with a limit of <30 min, content uniformity by USP <905>, and dissolution under USP <711> apparatus II at 50 rpm in 0.1 N hydrochloric acid. The same blend may also be filled into Size 3 hard gelatin capsules at an equivalent 200 mg fill weight. Published data for licensed 4-dimethylaminophenol tablet or capsule products remain limited; the stated platform parameters derive from general veterinary solid-dose development rather than a compendial monograph. The finished product type is a rapid-disintegration tablet or capsule for emergency oral administration in companion animal cyanide exposure kits.
For field-station reconstitution where bulk liquid handling is unsafe and cold-chain storage is absent, a dry powder or granule premix filled into foil sachets is used. The blend contains 5.0% w/w 4-dimethylaminophenol base equivalent on a lactose monohydrate carrier with 0.05% w/w citric acid as pH modifier and 0.01% w/w disodium edetate. Reconstitution of one 100 g sachet with 1 L potable water yields a nominal 5 mg/mL suspension, depending on water pH. Production uses low-shear tumble blending at 12 rpm for 20 min under <30% RH, with sieve size 500 µm for agglomerate removal before filling into four-layer aluminium-polyethylene sachets. Where dust control is critical, the blend is compacted into granules of 300–800 µm to improve flow and reduce airborne exposure. Blend uniformity follows Ph. Eur. 2.9.40, loss on drying is controlled by USP <731> or USP <921> with a moisture limit of <2.0% w/w, and the terminal finished product type is a powder or granule premix for extemporaneous oral administration to livestock.
When the same 4-dimethylaminophenol molecule is introduced at substoichiometric levels into multivitamin parenterals, it functions as a reducing oxygen scavenger rather than as the primary antidotal active. Incorporation at 0.05–0.2 mg/mL, equivalent to 0.005–0.02% w/v, is made after pH adjustment of the vitamin solution to 4.0–4.5 and before final nitrogen sparging; addition must not exceed 0.2% w/v to avoid interference with thiamine assay methods. The downstream process uses 316L stainless-steel mixing, 0.22 µm membrane filtration, and filling into amber Type I glass vials under nitrogen overlay. Stability-indicating assay methods follow ICH Q2(R1) or VICH GL2 validation principles, and final release complies with 21 CFR 211.166 and Ph. Eur. 5.1.1 sterility requirements for parenterals. Compatibility with thiamine, riboflavin, and ascorbic acid must be evaluated case-by-case; published data for this specific stabilizer configuration are limited. The terminal finished product type is a stabilized injectable multivitamin solution for veterinary administration.
Competitive 4-Dimethylaminophenol Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Product code VET-DMAP-01 identifies 4-dimethylaminophenol as a non-sterile veterinary active pharmaceutical ingredient manufactured under ICH Q7 good manufacturing practice and released against a non-compendial specification that aligns with VICH GL18 and VICH GL19. The substance is C8H11NO, CAS 619-60-5, relative molecular mass 137.18 g/mol. It is supplied as a white to off-white crystalline powder for further processing into tablets, injections, capsules, powders, granules, premix, and solutions. Two additional physical grades are assigned: VET-DMAP-02 micronized with D90 ≤ 30 µm, and VET-DMAP-03 low-endotoxin with a bacterial endotoxin limit of 0.25 EU/mg. Because no Ph. Eur., USP, or VICH harmonized monograph currently assigns acceptance criteria for 4-dimethylaminophenol, the certificate-of-analysis template is generated from validated in-house HPLC methods and Ph. Eur. general chapters for residual solvents, elemental impurities, and particulate behavior. The product is not terminally sterilized and is not released as sterile; any injection application must include a downstream aseptic filtration or terminal sterilization step supported by the marketing authorization holder.
The veterinary-grade material is differentiated at the point of manufacture by reactor control and purification. In the standard synthesis route, 4-aminophenol is subjected to reductive N,N-dimethylation in a glass-lined hydrogenation vessel, and the crude 4-dimethylaminophenol is recrystallized from an ethanol/water mixture. Recrystallization is monitored by inline HPLC with a photodiode array detector; lots are not pooled unless the total unknown impurity area remains below 0.50%. The solvent is removed under reduced pressure at a jacket temperature not exceeding 45 °C, because the solid melts at approximately 76–78 °C and rapid polymorphic transformation can occur near the melting point. Drying is performed in a vacuum tray dryer with a plate temperature below 40 °C until loss on drying is below 0.50%. Published data for the polymorphic landscape of veterinary-grade 4-dimethylaminophenol is limited; therefore the drying temperature is controlled conservatively to avoid generating a second crystal form that could alter dissolution rate in capsule or tablet formulations.
Photographic-grade 4-dimethylaminophenol is often released with a minimum assay value near 98.0% and is controlled for appearance and moisture only. It is not tested against VICH GL18 residual solvent classes, VICH GL19 unknown impurity thresholds, or Ph. Eur. 2.6.14 bacterial endotoxins. Such lots may contain free dimethylamine, nitroso intermediates, or solvent residues that are not declared. Veterinary-grade VET-DMAP-01 is controlled for total unknown impurities at ≤0.10% per single unspecified peak and ≤0.50% total related substances, with the meta isomer limited to ≤0.15% because its removal is the most difficult purification challenge. In comparison with 4-aminophenol, the N,N-dimethyl substitution gives a lower melting point, higher organic-solvent solubility, and different oxidative behaviour; therefore 4-dimethylaminophenol cannot be treated as a direct drop-in replacement for 4-aminophenol in a licensed veterinary formulation without revalidation.
| Parameter | VET-DMAP-01 veterinary grade | Photographic/technical grade | 4-Aminophenol reference |
|---|---|---|---|
| Assay by HPLC | 98.5–101.0% on anhydrous basis | commonly ≥98.0%, no related substance specification | not directly comparable; separate monograph required |
| Total unspecified impurities | ≤0.50% | not controlled | not controlled in industrial grade |
| Bacterial endotoxins | <0.25 EU/mg for VET-DMAP-03 | not tested | not applicable |
| Residual solvents | VICH GL18, headspace GC-FID | not addressed | not addressed |
| Particle-size control | D90 ≤ 150 µm; micronized ≤ 30 µm | not controlled | not controlled |
Release tests are selected according to the intended downstream dosage form. Tablets and capsules require particle-size control, flow characterization, and low residual solvent burden. Injections require a defined endotoxin limit, sub-visible particulate counts after reconstitution in water for injection, and absence of visible foreign matter. Premix and powder applications require a narrower particle-size distribution because poor flow and segregation can produce superpotent pockets; a sieved fraction above 250 µm is limited to ≤1.0% for the standard grade and ≤0.2% for the micronized grade.
| Parameter | Acceptance criterion | Analytical procedure |
|---|---|---|
| Appearance | White to off-white crystalline powder | Visual |
| Identification by IR | Matches reference spectrum | Ph. Eur. 2.2.24 |
| Assay by HPLC | 98.5–101.0% on anhydrous basis | In-house HPLC, UV detection at 254 nm |
| Loss on drying | ≤0.50% | Ph. Eur. 2.2.32 |
| Residue on ignition | ≤0.10% | Ph. Eur. 2.4.14 |
| Related substances total | ≤0.50% | In-house HPLC area normalization |
| Single unspecified impurity | ≤0.10% | In-house HPLC area normalization |
| Meta isomer 3-dimethylaminophenol | ≤0.15% | In-house HPLC |
| Residual solvents | Ethanol ≤5000 ppm, methanol ≤3000 ppm, dichloromethane ≤600 ppm | VICH GL18 / Ph. Eur. 2.4.24 |
| Elemental impurities | Meets VICH GL19 for oral and injectable veterinary dosage forms | ICP-MS |
| Bacterial endotoxins, VET-DMAP-03 only | <0.25 EU/mg | Ph. Eur. 2.6.14 |
| Particle size D90, standard | ≤150 µm | Laser diffraction, ISO 13320:2020 |
| Particle size D90, micronized | ≤30 µm | Laser diffraction, ISO 13320:2020 |
4-Dimethylaminophenol is electron-rich and undergoes oxidative discoloration in aqueous solution when dissolved oxygen exceeds 0.1 mg/L or when the solution headspace contains more than 5% v/v oxygen. In a solution dosage form, the pH is usually adjusted to between 3.5 and 5.5 with hydrochloric acid or citric acid to maintain the tertiary amine in its protonated, water-soluble state; the free base has lower water solubility and is more sensitive to oxidation. Degradation produces quinonoid oligomers with a pink-to-brown chromophore. The reaction accelerates in the presence of trace iron and copper at concentrations above 0.1 ppm; therefore chelating agents such as disodium edetate may be added at 0.05–0.10% w/v, but only after compatibility with the primary container is confirmed under ICH Q1B photostability. Nitrogen sparging to dissolved oxygen ≤0.05 mg/L before filling and amber glass with low iron content are standard control measures for parenteral and oral solution batches. Terminal sterilization by autoclaving at 121 °C for 15 min is not universally applicable because the molecule can degrade if the solution pH is above 6.0; the marketing authorization holder must generate pH-dependent stability data for the specific formulation. Published data for this specific configuration is limited; stability results from the formulation itself are therefore release-controlling.
Residual solvent control follows VICH GL18. Recrystallization from ethanol/water leaves ethanol as the principal Class 3 solvent; methanol and dichloromethane are included only if the manufacturing route uses them in a preceding step. Limits are set at ≤5000 ppm ethanol, ≤3000 ppm methanol, and ≤600 ppm dichloromethane. Solvent content is measured by headspace gas chromatography with flame ionization detection on every batch. Elemental impurity control follows VICH GL19 for veterinary drug substances intended for parenteral and oral administration; routine ICP-MS screening includes lead, cadmium, arsenic, mercury, cobalt, vanadium, and nickel. Release data from three consecutive validation batches are required to establish a process capability index above 1.33 for the lead limit before the material may be considered for commercial release. The material should not be stored in uncoated copper or iron vessels because the phenolic hydroxyl group can coordinate metal ions and darken the powder; stainless steel 316L or glass-lined equipment is specified for all product-contact surfaces.
On production-scale tablet lines, the standard powder is preferably processed by wet granulation rather than direct compression because the crystalline material has low compactibility and may cap at compression pressures above 12 kN on a single-punch press. In a rotary tablet press operating at 50 rpm with a 10.0 mm round flat-faced punch, tablets containing mannitol and microcrystalline cellulose can meet Ph. Eur. 2.9.8 resistance to crushing and Ph. Eur. 2.9.3 disintegration when granulate moisture is held at 2.0–3.0% w/w during compression. Dry conditions below 1.5% moisture may increase picking and sticking on the punch faces. For capsules, dosator or tamping-pin machines require fill weight uniformity under Ph. Eur. 2.9.5; bulk density can shift from 0.28 g/mL to 0.42 g/mL across crystallization lots if vacuum drum drying is not tightly controlled. A flow aid at 0.5–1.0% w/w colloidal silicon dioxide is generally necessary to keep capsule fill weight variation within acceptance limits at speeds above 30,000 capsules/h.
For injections, the low-endotoxin grade VET-DMAP-03 is dissolved in water for injection at a concentration determined by the authorized formulation. The solution is filtered through a 0.45 µm polyethersulfone membrane followed by a 0.22 µm membrane as the sterilizing grade filter; filter compatibility is validated because the phenolic amine can extract certain membrane wetting agents at low pH. Terminal autoclaving may be used only when stability data demonstrate no increase in related substances above 0.2% at the maximum processing temperature. Sub-visible particulate counts should comply with Ph. Eur. 2.9.19 and USP 788 for the chosen container, but the API is released as a raw material and cannot confer final dosage form compliance without terminal filtration and filling validation.
Dry blending into a feed premix requires humidity control. The powder exhibits electrostatically assisted agglomeration at relative humidity below 30% RH, causing segregation of the ≤75 µm fraction during pneumatic conveying. Production-scale batches in a 1000 L ribbon blender operated at 12 rpm for 20 min can meet Ph. Eur. 2.9.40 uniformity of dosage units when the API is screened through a 500 µm sieve before charging and the blender is earthed. If the formulation contains fatty acid salts or acidic carriers below pH 3.0, local discoloration occurs at contact points; such formulations require a sealed high-shear premix rather than prolonged ribbon blending.
The API is double-bagged in low-density polyethylene and packed in fibre drums with an aluminium barrier liner. Storage at 15–25 °C in a dry environment below 60% RH is specified; opened containers should be resealed under nitrogen because the powder can darken on prolonged exposure to air. Under VICH GL11, a retest interval of 24 months may be proposed when long-term data at 25 °C/60% RH and accelerated data at 40 °C/75% RH show no significant change in assay, related substances, moisture, or appearance. The material should not be shipped in the same container as oxidizing agents or volatile amines; incompatible transport conditions can shift the impurity profile before processing.
