Cefquinome Intramammary Infusion Veterinary Grade API for Tablets / Injections / Capsules / Powders / Granules / Premix / Solutions is the sulfate salt of cefquinome, a fourth-generation cephalosporin supplied as a white to off-white crystalline powder. The CAS registry number for the sulfate salt is 118443-89-3; the free acid has the molecular formula C23H24N6O5S3 and a relative molecular mass of 560.4 g/mol. The material is an active pharmaceutical ingredient, not a finished intramammary syringe or ready-to-administer solution. No universal product model designation applies across manufacturers. Identification and traceability are controlled by batch number, assigned retest date, and the approved manufacturer certificate of analysis. The API is intended for the manufacture of licensed veterinary medicinal products under Part II of the EU Guide to Good Manufacturing Practice for active substances, and sterile dosage forms require compliance with EU GMP Annex 1 or equivalent national standards.

Chemical substitution differentiates cefquinome from earlier veterinary cephalosporins. The molecule carries an aminothiazolyl methoxyimino acetyl side chain at C-7 and a 5,6,7,8-tetrahydroquinolin-2-yl thioether at C-3. That arrangement assigns the compound to the fourth-generation cephalosporin class and reduces the affinity of the molecule for many plasmid-mediated and AmpC β-lactamases. In contrast, ceftiofur is a third-generation cephalosporin that undergoes rapid biotransformation to desfuroylceftiofur, whereas cefquinome is not dependent on that metabolite pathway for antibacterial activity. Cefoperazone belongs to the third-generation class and has a different C-3 dioxopiperazine substituent; it is not an appropriate reference for cefquinome susceptibility breakpoints. The current CLSI document VET01S should be consulted for interpretive criteria rather than transferring ceftiofur or cefoperazone breakpoints.

Storage boundaries for the API are set by the hydrolysis sensitivity of the β-lactam ring. Sealed, light-resistant containers should be kept at ≤25 °C and ≤40 % RH. Above RH 60 %, adsorbed moisture initiates hydrolytic ring opening; alkaline aqueous media above pH 8.0 and acidic media below pH 3.0 both accelerate degradation. In dispensing suites, open handling time should not exceed 8 h unless the environment is maintained at ≤30 % RH and ≤25 °C. Strong oxidizing agents, mineral acids, and primary amine additives are incompatible with the cephem nucleus. Preblends with amine-containing feed additives are contraindicated unless compatibility is confirmed by HPLC assay after a 48 h challenge at 40 °C/75 % RH.

Bulk powder testing includes appearance, assay on dried basis, water content, related substances, residual solvents, and bacterial endotoxins for parenteral and intramammary grades. The API should be sampled according to ISO 2859-1 or an equivalent risk-based sampling plan. Containers are closed with low-moisture-transmission closures. The material should not be returned to the original container after scooping unless a dedicated sampling thief is used under laminar flow. Dedicated or campaign-based processing is standard because residual β-lactam cross-contact is unacceptable in non-β-lactam products. Cleaning procedures should be validated to a carryover limit that does not exceed the lowest therapeutic dose of any subsequent product.

Does the Same API Lot Suit Both Injectable and Non-Sterile Oral Dose Forms?

No single cefquinome sulfate API grade is automatically suitable for all dosage forms. Injectable and intramammary infusion manufacture requires a parenteral-grade specification with bacterial endotoxin control at <0.05 EU/mg by Ph. Eur. 2.6.14, and the finished container must meet the sterility test of Ph. Eur. 2.6.1. Non-sterile oral powders, granules, tablets, capsules, and premixes can be produced from an oral-grade material with less stringent endotoxin limits, but content uniformity and particle size then become the limiting quality attributes. A lot assigned to aseptic parenteral manufacture cannot be downgraded to oral use if the container integrity has been compromised. Conversely, oral-grade material must not be reprocessed into parenteral products because endotoxin removal is not validated during dissolution or blending; ultrafiltration of the API solution may reduce pyrogens but is not a substitute for controlled manufacture.

Route-specific grades are shown in the following matrix. The limits are representative and must be aligned with the finished-product marketing authorization.

For tablets and capsules, dry processing is preferred over wet granulation. Roller compaction with a 20/80 mesh granulate fraction and API particle size D90 ≤75 µm improves content uniformity without exposing the compound to aqueous granulation fluids. Direct compression may be acceptable when the API load is below 30 wt% and excipients are selected for low moisture, typically microcrystalline cellulose and pregelatinized starch. Magnesium stearate should be limited to ≤1.0 wt% and the final blend time to ≤5 min to avoid excessive hydrophobic film formation that delays disintegration. Tablet hardness is defined by the dissolution profile of the finished product rather than by intrinsic API requirements. Hard-shell capsule filling requires free-flowing granules with angle of repose ≤35°; soft gelatin capsules are generally unsuitable unless the fill mass is anhydrous and the shell water activity is below 0.40, because water migration degrades the β-lactam ring.

Granulation by fluid-bed processing is used only when the formulation design requires it. The inlet air dew point should be ≤−10 °C and product temperature ≤35 °C; alkaline binders such as sodium bicarbonate destabilize the β-lactam ring and must be avoided. Dried granules are milled through a 1.0 mm screen and lubricated before encapsulation or tableting. The moisture after drying is controlled at ≤2.0 % by Karl Fischer titration. If the granulation solvent contains water, drying time in a tray dryer should not exceed 4 h at 40 °C unless the process is validated for the specific batch size. Tablet weight variation should be checked according to Ph. Eur. 2.9.5 and content uniformity according to Ph. Eur. 2.9.6.

Release Specification and Stability-Indicating Method Parameters

A representative release specification for parenteral and intramammary cefquinome sulfate API appears below. Limits are indicative values; the registered dossier and current pharmacopoeial monograph take precedence for the approved product.

Stability-indicating HPLC methods for cefquinome sulfate should separate the parent peak from major hydrolysis products and the sulfate counterion. A C18 column with a mobile phase of phosphate buffer and acetonitrile at pH 6.5 and detection at 254 nm is commonly used. Validation follows ICH Q2(R2) for specificity, linearity, accuracy, precision, and range. Forced degradation with 0.1 M HCl, 0.1 M NaOH, and 3 % hydrogen peroxide provides stress data; mass balance should be reported. If any unspecified impurity exceeds 0.15 % in accelerated stability studies at 40 °C/75 % RH, the degradation pathway must be investigated under ICH Q1A(R2). Sulfate content should be confirmed by ion chromatography or equivalent compendial method. Potency may also be determined by microbiological agar diffusion assay, but HPLC is preferred because of specificity for the intact β-lactam ring.

Commercial synthesis of cefquinome sulfate is based on acylation of the 7-aminocephalosporanic acid nucleus with an activated aminothiazole methoxyimino side chain, followed by introduction of the tetrahydroquinolinyl thioether at C-3. Crystallization and salt formation with sulfuric acid produce the sulfate salt. Residual solvents from the synthesis may include methanol and N,N-dimethylformamide; these are controlled by ICH Q3C Class 2 limits. The API is then micronized or classified to the agreed particle size. Published data for this specific configuration is limited, so batch-scale process validation must demonstrate reproducibility across at least three consecutive commercial batches.

Injectable solutions should be filled aseptically into Type I glass vials or polymer containers meeting Ph. Eur. 3.2.1 and 3.2.2. Headspace oxygen can promote degradation; nitrogen overlay to residual oxygen ≤5 % is common. The finished solution should be stored at 2–8 °C unless the dossier demonstrates room-temperature stability. For parenteral solution manufacture, the sulfate salt is dissolved in Water for Injection, with pH adjusted to 5.5–7.0 using dilute sodium hydroxide or hydrochloric acid. Below pH 4.0, degradation rate increases; above pH 8.0, β-lactam ring opening is accelerated. Terminal steam sterilization at 121 °C for 15 min is generally not used for cefquinome finished injections because the hydrolytic degradation products can exceed the finished-product specification; aseptic filtration through a 0.22 µm polyethersulfone membrane is the standard approach. Published data for this specific terminal sterilization configuration is limited, so each manufacturer must generate worst-case heat-stability data for the chosen formulation.

When the API Is Dispersed for Intramammary Syringes or Aqueous Premix Solutions

For intramammary suspension syringes, cefquinome sulfate is dispersed in an anhydrous oily vehicle or a low-water-activity gel. Micronization to D90 ≤20 µm is specified to prevent needle obstruction and to maintain a uniform suspended solid during manual inversion. Aseptic filling of prefilled syringes takes place in Grade A conditions with crimped closure integrity verified by dye ingress or vacuum decay testing. A lactating cow product may contain 75 mg cefquinome per 8 g intramammary dose, but the approved label controls the exact strength and dosing interval. The API supplier does not set withdrawal periods; those are assigned by the finished-product regulatory file based on tissue and milk residue depletion studies.

For aqueous premix solutions, the sulfate salt is dissolved in potable water at the lowest practical concentration. The solution should be used within 24 h at room temperature and protected from direct sunlight; above pH 7.5 or below pH 3.0, degradation accelerates. Hard water containing more than 500 ppm calcium carbonate equivalent can reduce dissolution and should be softened before mixing. Stock solutions are not recommended for prolonged holding; refrigerated storage at 2–8 °C may be acceptable for 48 h if protected from light and supported by HPLC stability data. Once diluted in a header tank, the solution should not be mixed with alkaline concentrates, oxidizing disinfectants, or other antimicrobials unless compatibility is demonstrated by assay and physical observation.

Powders for oral solution are prepared by blending the API with dextrose anhydrous or lactose monohydrate and a desiccant sachet inside the final container. The powder should be dissolved with stirring for 10 min and consumed within 24 h. For feed premixes, the API is diluted geometrically with lactose or dextrose using a horizontal ribbon blender with working capacity 50–80 % and tip speed 1–2 m/s. Mixing for 15–20 min is typically sufficient when the active fraction is above 1 wt%; below that, a pre-blend is required and the final premix should be sampled across at least 10 points for assay. Once mixed with molasses-based carriers, the premix should be consumed within 48 h unless valid stability data support longer storage.

Compared with ceftiofur sodium, cefquinome has a different residue marker profile and does not rely on desfuroylceftiofur metabolite formation for microbiological activity. Compared with cefoperazone, cefquinome is reserved for veterinary medicine and must not be compounded for human use. In food-producing species, the approved finished product defines meat and milk withdrawal periods; these are mandatory and vary by route, dose, formulation, and national regulatory status. The API should be handled as a β-lactam sensitizer; personnel with cephalosporin allergy should avoid skin contact and airborne powder exposure. Dedicated equipment and validated cleaning procedures are required because trace β-lactam carryover can contaminate non-β-lactam products and trigger anaphylactic reactions in exposed patients. No additional performance claims should be made without a validated finished-product registration file.