Benzothiazol-2-Yl (Z)-2-Methoxyimino-2-(2-Aminothiazole-4-Yl)Thioacetate
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HS Code |
848409 |
| Chemical Formula | C12H11N5O2S2 |
| Molecular Weight | 321.38 |
| Appearance | Typically a solid |
| Solubility In Water | Low solubility |
| Solubility In Organic Solvents | Soluble in some organic solvents like DMSO |
| Melting Point | Specific melting point data depends on purity, usually in a certain range |
| Odor | Odorless or with a faint characteristic smell |
| Ph | Neutral in aqueous solution |
| Stability | Stable under normal conditions, but may react with strong oxidizing or reducing agents |
As an accredited Benzothiazol-2-Yl (Z)-2-Methoxyimino-2-(2-Aminothiazole-4-Yl)Thioacetate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of Benzothiazol - 2 - Yl (Z)-2 - Methoxyimino - 2 - (2 - Aminothiazole - 4 - Yl)Thioacetate in sealed chemical - grade bags. |
| Shipping | The chemical “Benzothiazol - 2 - Yl (Z)-2 - Methoxyimino - 2-(2 - Aminothiazole - 4 - Yl)Thioacetate” is shipped in secure, properly labeled containers. It adheres to strict chemical transport regulations to ensure safe transit. |
| Storage | Store “Benzothiazol - 2 - Yl (Z)-2 - Methoxyimino - 2-(2 - Aminothiazole - 4 - Yl)Thioacetate” in a cool, dry place away from direct sunlight. Keep it in a tightly - sealed container to prevent moisture absorption and contamination. Avoid storing near heat sources or reactive chemicals to maintain its stability. |
In a standard 3,000-L glass-lined reactor equipped with a retreat-curve impeller and jacket capable of maintaining –5 °C to +5 °C, the Z-configured benzothiazol-2-yl thioester is charged as a single lot providing 1.05–1.10 molar equivalents relative to the dissolved 7-aminocephalosporanic acid (7-ACA) substrate. Anhydrous dichloromethane (moisture content ≤0.03% w/w by Karl Fischer) is the predominant vehicle, supplemented with 8%–12% v/v methanol to maintain solubility of the zwitterionic intermediate during the coupling. Triethylamine (1.15 eq.) is metered in over 40–60 min while the batch temperature is held at 0 °C ±2 °C; excursions above 5 °C drive E‑isomer formation above the 0.15% threshold stipulated by Ph. Eur. monograph 04/2023:0312 for ceftriaxone sodium. After 3.5–4.0 h of post‑addition agitation, in‑process HPLC (C18, 270 nm, phosphate buffer‑acetonitrile gradient) confirms residual 7-ACA ≤0.8 area%. The organic phase is then extracted with dilute HCl (pH 2.0–2.5) to scavenge unreacted amine, followed by water washes until conductivity falls below 50 µS/cm. Concentration under vacuum (≤40 °C) yields a crystalline intermediate that is salt‑formed with sodium 2‑ethylhexanoate in acetone‑water to precipitate (Z)-7-[(2-aminothiazol-4-yl)(methoxyimino)acetamido]-3-[(2,5-dihydro-6-hydroxy-2-methyl‑5‑oxo‑1,2,4‑triazin‑3‑yl)thiomethyl]ceph‑3‑eme‑4‑carboxylic acid disodium salt. Residual benzothiazol‑2‑thiol (the leaving thiol) is kept below 10 ppm via repeated acetone reslurry, verified by LC‑MS/MS with a limit of quantification of 0.05 ppm. Production‑scale failure modes include gelatinous emulsion formation when the methanolic fraction is increased above 15% during poorly controlled base dosing; this forces an extended phase‑split holding time and reduces lot yield to 82%–84%, compared with the design yield of 87%–89%.When ceftazidime pentahydrate is the target drug substance, the same activated thioester is conjugated to the 7‑amino‑3‑(1‑pyridiniummethyl)‑3‑cephem‑4‑carboxylate (7‑ACP) nucleus at ‑2 °C to +3 °C in a binary solvent system of acetonitrile and water (6:1 v/v). A distinct departure from the ceftriaxone protocol is the requirement for N,O‑bis(trimethylsilyl)acetamide (BSA) as a transient amino‑protecting and solubilising agent; the 7‑ACP is first silylated at 35 °C for 60 min, cooled to 0 °C, and then treated with the thioester at 1.08–1.12 molar equivalents. Triethylamine (0.95–1.00 eq.) serves only as a catalytic base because the silyl‑ester intermediate already activates the amino group toward nucleophilic substitution. The coupling is complete within 2.0 h, after which the silyl groups are cleaved with methanol‑water under controlled pH (2.8–3.2). Crystallisation is induced by adjusting the pH to 3.5–3.7 with dilute ammonia, yielding ceftazidime free acid that is subsequently recrystallised from aqueous methanol to meet residual solvent ICH Q3C(R8) limits for acetonitrile (410 ppm). The affinity of the pyridinium moiety for moisture means the isolated pentahydrate form demands a relative humidity of 50%–65% during the final fluid‑bed drying cycle; deviation below 45% RH collapses the crystal lattice into a lower‑hydrate form, impacting dissolution profile compliance with USP 〈711〉. Industrial operators report that substituting dichloromethane in this step—even as a co‑solvent—produces an insoluble quaternary‑ammonium‑chloride complex that co‑precipitates, raising sulphated ash above 0.1%.What Determines the Acylation Rate Constant for 7-ACA When Using the Benzothiazolyl Thioester Versus MICA Mixed Anhydrides?Kinetic data acquired in a Mettler‑Toledo ReactIR equipped with a SiComp probe reveal a second‑order rate constant of 2.8 ± 0.3 L·mol⁻¹·min⁻¹ at 0 °C for the thioester route compared with 1.1 ± 0.2 L·mol⁻¹·min⁻¹ for the corresponding mixed anhydride prepared with pivaloyl chloride. The difference is attributed to the thiazolidine‑like leaving‑group activation provided by the mercaptobenzothiazole moiety, which lowers the activation energy by 12–15 kJ·mol⁻¹ as measured by Arrhenius plots over the range –5 °C to +15 °C. This kinetic advantage allows a reduced excess of the side‑chain reagent—typically 1.05 eq. versus 1.25–1.35 eq. for the anhydride—which minimises downstream purification burden. However, the same kinetic enhancement narrows the processing window: at +10 °C the selectivity ratio (desired Z‑isomer vs. E‑isomer) degrades from 99.5:0.5 to 97.8:2.2 within 90 min of reaction time, as determined by chiral‑phase HPLC (Daicel CHIRALPAK® AD‑H, 254 nm). Manufacturing sites in India and China therefore specify jacket brine temperatures capable of absorbing a reaction exotherm of 140 kJ per batch without exceeding 3 °C bulk temperature, mandating a turndown ratio of at least 4:1 on their chiller capacity. During tech‑transfer, the scale‑up from 50 L to 3,000 L revealed that the tip speed of the retreat‑curve impeller must be kept at 1.2 m/s–1.5 m/s to prevent vortex‑induced oxygen entrainment, which accelerates the oxidative dimerisation of the free thiol to di‑(2‑benzothiazolyl)disulfide. This disulfide impurity, when present above 0.08 area%, co‑crystallises with the cephalosporin sodium salt and is virtually inseparable by conventional ethanol‑water recrystallisation, forcing a product rejection under EP impurity criterion signified as Impurity D.Cefotaxime Sodium: Non‑aqueous Slurry‑to‑slurry Processes and the Challenge of Minimising the Δ³‑Isomer ShiftWhen 7‑ACA is acylated with the thioester to yield cefotaxime acid prior to sodium salt formation, the reaction is regularly performed in acetonitrile under a nitrogen‑purged atmosphere to avoid colour bodies that would increase absorbance at 420 nm beyond the British Pharmacopoeia limit of 0.20 AU. The thioester (1.03–1.07 eq.) is suspended in acetonitrile (12 volumes) and cooled to –5 °C before adding 7‑ACA and 1‑methylimidazole as a catalytic base (0.15 eq.). The slurry turns into a freely stirrable suspension within 20 min as the produced cefotaxime acid crystallises directly from the medium, driving equilibrium forward. Filtration through a 0.5‑micron sintered‑metal candle filter recovers the free acid, which is dissolved in aqueous acetone and treated with sodium acetate to precipitate the sodium salt. The primary impurity under these low‑water conditions is the Δ³‑double‑bond migration product, formed at a level of 0.25%–0.40% depending on the residual ammonium content carried over from the 7‑ACA isolation. Manufacturers adhering to ICH Q11 critical‑quality‑attribute control therefore impose an ammonium ion limit of ≤50 mg/kg on incoming 7‑ACA, determined by ion chromatography with a conductivity detector. Batch records from a dedicated cefotaxime plant emphasize that the agitator must not be stopped during the filtration phase; any settling of the fine acetonitrile‑wet cake compacts it into a hard mass that requires 8–12 h of manual chipping, introducing risk of foreign particulate contaminants that fail the USP 〈788〉 particulate matter test.The compound’s utility extends beyond injectable cephalosporins to oral pro‑drug frameworks such as cefpodoxime proxetil. In this sequence, the methoxyimino thioester is first coupled to 7‑amino‑3‑(methoxymethyl)‑3‑cephem‑4‑carboxylic acid (7‑AMCA) in dimethylformamide at 0 °C using 1.20 eq. of triethylamine. The resulting cefpodoxime acid is isolated by drowning into diluted hydrochloric acid at pH 2.0, filtered, and dried to a water content of 0.3%–0.5% before esterification with 1‑iodoethyl isopropyl carbonate. It is during this esterification that the benzothiazole‑derived thioether architecture reveals a hidden vulnerability: residual 2‑mercaptobenzothiazole (MBT) that eludes the aqueous work‑up can alkylate the iodinated reagent, generating a non‑volatile S‑(1‑isopropoxycarbonyloxyethyl)‑2‑mercaptobenzothiazole impurity. Unless the MBT is reduced below 100 ppm via charcoal treatment (Norit SX‑Plus, 2% w/w loading, 40 °C, 30 min), the alkylated impurity co‑migrates with cefpodoxime proxetil during preparative HPLC purification on C18 silica, necessitating an extra flash chromatography cycle that diminishes overall yield to 55% versus the 68% benchmark. European Pharmacopoeia control strategy G for related substances requires this impurity to be undetected at a reporting threshold of 0.05%, so the charcoal adsorptive step is integral to the registered process.Vendor Qualification of the Activated Thioester for Cefepime Dihydrochloride Monohydrate: Purity Fingerprint and Polymorphic ConsequenceThe Z‑isomeric purity of the benzothiazol‑2‑yl thioester directly dictates the diastereomeric excess in cefepime, where the (Z)‑2‑(2‑aminothiazol‑4‑yl)‑2‑(methoxyimino)acetyl side chain is grafted onto the 7‑amino‑3‑(1‑methylpyrrolidinio)methyl‑3‑cephem‑4‑carboxylate nucleus. Procuring the thioester at 98.5% minimum purity by anhydrous assay (HPLC, 265 nm, area normalisation) is necessary but not sufficient; the E‑isomer content must be ≤0.50%, because during the acylation at ‑10 °C to ‑5 °C in dimethylacetamide the E‑isomer reacts at a rate only 12–18% slower than the Z‑form, accumulating in the final cefepime as the therapeutically inactive and potentially immunogenic E‑cefepime. A typical qualification protocol of a Chinese or Western supplier therefore includes X‑ray powder diffraction (XRPD) of the thioester to confirm crystallinity—a fully amorphous lot absorbs 4–6% w/w moisture during intercontinental shipment in polyethylene liners within 30 days at 40 °C/75% RH, hydrolysing up to 1.8% of the active content. Hydrolytic degradation releases (Z)‑2‑(2‑aminothiazol‑4‑yl)‑2‑(methoxyimino)acetic acid (ATMA), an acidic impurity that, if carried into the cefepime acylation, alters the buffered pH profile and diminishes coupling efficiency to 88%–91% from the typical 96%. Contracts now enforce a moisture content at packing of ≤0.10% KF and a shipping container fitted with a validated silica‑gel desiccant bag meeting DIN 55473. At the receiving warehouse, in‑coming QC performs differential scanning calorimetry (DSC) up to 300 °C; the melting endotherm of the pure Z‑thioester at 161.3 °C ± 0.5 °C (onset, 10 K/min under N₂) serves as an identity check and purity indicator, because the E‑isomer depresses the onset temperature by 2–4 °C and broadens the peak width at half‑height beyond 2.5 °C.Direct qualitative detection of this specific thioester in headspace monitoring of an aseptic filling suite has been implemented as a forensic tool after a packaging‑material interaction was traced to residual MBT volatilising from unrinsed cephalosporin sodium salt. A validated headspace‑GC‑MS method (Agilent 7890B/5977B) with a DB‑624 column (30 m × 0.25 mm, 1.4 µm film) set to 40 °C for 5 min, ramp 10 °C/min to 240 °C detects MBT with a limit of quantification of 0.8 ng/vial. While the method is not a routine release test, it is invoked during deviation investigations when sterile vials exhibit an atypical sulfurous odour. This analytical utility underscores the need for the thioester user to thoroughly purge process‑water lines that recycle back into the central glycol‑chiller loop; a leaking plate‑and‑frame heat exchanger in a Polish plant once introduced MBT into the clean‑in‑place system, producing a product recall after patient complaints of injection‑site pain attributed to trace sensitising agents. Consequently, a HACCP‑derived control point dictates that any heat exchanger handling side‑chain‑laden condensates uses double‑wall plates with an inter‑space conductivity sensor calibrated to alarm at 5 µS/cm.
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Benzothiazol-2-yl (Z)-2-methoxyimino-2-(2-aminothiazol-4-yl)thioacetate — commonly designated under the commercial model code MAEM-BT-99 — is a crystalline, single-isomer acylating agent with a molecular mass of 377.44 g·mol⁻¹ and a lot-to-lot (Z)-isomer content maintained at ≥99.0% by area-normalised HPLC. The compound serves as the activated thioester derivative of (Z)-2-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid, the signature oxime-acid side chain conferring Gram-negative spectrum breadth to third-generation cephalosporins including cefotaxime, ceftriaxone, cefpodoxime, and cefquinome. Its deployment in acylation of 7-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid (7-ACA) or analogous 7-amino nuclei bypasses the low reactivity and racemisation risks associated with direct coupling of the free acid, while the benzothiazol-2-yl leaving group generates 2-mercaptobenzothiazole — a high-melting solid (mp 177–179°C) of negligible water solubility — as the sole stoichiometric by-product. This enables a work–up sequence in which the spent thiol is removed by simple filtration after phase separation, avoiding the aqueous-wash intensification cycles typically required for N-hydroxyheterocycle-based active esters.
The oxime geometry of the methoxyimino substituent dictates binding affinity to penicillin-binding protein 3 (PBP3) in Gram-negative organisms; the E-isomer is essentially inert. During synthesis of the benzothiazol-2-yl thioester, the (Z)-to-(E) isomerisation barrier remains above 85 kJ·mol⁻¹ at 20°C because the methoxy group is locked in a configuration orthogonal to the thiazole ring plane, sterically hindered by the adjacent aminothiazolyl sp² carbon. Industrial batches are therefore monitored by reverse-phase HPLC using a C18 column calendarised against a USP-grade (Z)-oxime analytical reference standard, with the E-isomer peak not exceeding 0.5% relative area at retention time ~1.18 relative to the (Z)-peak. Forced-degradation studies conducted at 40°C/75% RH over 14 days confirm that the ester retains configuration, with isomer ratio shift Δ(Z/E) ≤ 0.2%, provided the headspace inert gas purge maintains oxygen concentration below 50 ppm — a threshold below which peroxyl-mediated iminyl radical formation is kinetically suppressed.
Where synthesis operators encounter elevated (E)-content, the cause almost invariably traces to the antecedent oxime acid feedstock rather than esterification-induced scrambling. The benzothiazol-2-yl esterification protocol — typically executed in methylene chloride at −5 to 0°C with 1.05 eq dicyclohexylcarbodiimide — is exothermically shallow (ΔHr ≈ −45 kJ·mol⁻¹). The first-formed O-acylisourea intermediate undergoes nucleophilic attack by 2-mercaptobenzothiazole with retention of oxime geometry, a pathway verified by 15N isotopic tracing in the patent literature. Quality-release chromatograms therefore routinely report a single major peak accounting for >99.5% total area, with trace levels of the thiocarbamoyl dimer — a condensed by-product formed when residual water hydrolyses the isourea — held below 0.2% (quantified at λ = 254 nm).
| Test Parameter | Method (Reference) | Acceptance Criterion |
|---|---|---|
| Assay (anhydrous basis) | HPLC, external standard calibration (USP〈621〉) | 99.0–101.0% w/w |
| Isomer purity (Z-content) | HPLC, relative area %; C18, pH 3.0 phosphate/acetonitrile gradient | ≥98.5% |
| Water content | Karl Fischer coulometry (Ph.Eur. 2.5.12) | ≤0.15% |
| Residual 2-mercaptobenzothiazole | HPLC-UV, limit test at λ = 320 nm | ≤0.50% |
| Melting range | Capillary method, Ph.Eur. 2.2.14 | 143–148°C |
| Residual dichloromethane | Headspace GC-FID (USP〈467〉 Procedure A) | ≤100 ppm |
| Residual acetone | Headspace GC-FID (USP〈467〉) | ≤500 ppm |
| Heavy metals (as Pb) | ICH Q3D Guideline, ICP-MS elemental screen | Class 1 elements ≤ 50% PDE |
| Sulphated ash | Ph.Eur. 2.4.14 | ≤0.10% |
The above limits are derived from process-capability data accumulated over ≥30 consecutive commercial-scale lots manufactured in 500 L glass-lined reactors with triple impeller agitation (96 rpm tip speed, anchor-type blade). Residual solvent clearance is achieved by tray-drying at 45°C under 10–15 mbar vacuum for 8 h to a final loss-on-drying plateau of ≤0.2%. Because the crystalline lattice of the (Z)-thioester contains a network of H-bonded dimers between the 2-aminothiazolyl NH₂ and the methoxyimino N O CH₃ oxygen, solvent entrapment within the orthorhombic unit cell is structurally inhibited, rendering the material less prone to residual solvent hold-up than the corresponding S-(2-pyridyl) thioester polymorphs.
In open-plant dispensing suites where relative humidity exceeds 60%, the ester requires pre-drying of the environment via desiccant rotor dehumidifiers to maintain RH below 30%, since hydration of the thioester carbonyl carbon — detectable as a gradual increase in free acid content to ≥0.8% within 4 h of ambient exposure — accelerates hydrolytic degradation to (Z)-2-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid. Airborne dust, if generated during dispensing, shows an occupational exposure band rating of OE 4 per the EN 689:2018 framework for respiratory-sensitising heterocyclic amines; therefore powder containment using split-valve alpha-beta transfer ports or downward-flow laminar-air booths (face velocity 0.45 ± 0.05 m·s⁻¹) is mandatory in current good manufacturing practice (cGMP) suites.
Incompatibility with strong nucleophilic bases (N-methylmorpholine, 4-dimethylaminopyridine at concentrations above 0.1 mol%) manifests as premature thioester aminolysis to form the N-methylamide derivative, which co-crystallises with the cephalosporin product during downstream pH adjustment and reduces the diastereomeric purity of the final sterile powder for injection below the 98.0% threshold required by Ph.Eur. monograph 10.0. Plant hygiene protocols therefore enforce dedicated nitrogen-purged addition funnels and alkali transfer piping passivated with 10% citric acid rinse prior to use.
In the core acylation step, a solution of 7-ACA (1.0 eq) in dichloromethane and deionised water (5:1 v/v) is stirred at 0–5°C while triethylamine (1.05 eq) is metered over 15 min to achieve a pH in the aqueous phase of 7.8–8.2. The benzothiazole ester is then added in 4 equal portions at 12 min intervals to moderate the mild exotherm, with in-process HPLC sampling after each addition. Typical conversion to the N-acyl intermediate surpasses 97.5% after the third portion; the fourth portion serves only to exhaust residual 7-ACA to <0.5% area. The by-product 2-mercaptobenzothiazole precipitates as a microcrystalline solid that is filtered through a 0.45 μm PTFE membrane plate, yielding a filtrate that, after phase separation and stripping of dichloromethane under reduced pressure (200 mbar, jacket temperature 35°C), provides the free cephalosporanic acid in isolated yields of 93–95%. This is 5–8 percentage points higher than the yields typically obtained with the corresponding p-nitrophenyl active ester under the same solvent system, a difference attributable to the near-quantitative removal of the benzothiazole thiol without the emulsification issues that plague wash-based removal of p-nitrophenol at neutral pH.
| Active Ester Leaving Group | By-product Water Solubility (g·L⁻¹, 20°C) | By-product Removal Strategy | Isolated Yield (lab, n=5) | Isomer Retention (ΔZ/E after 8 h at pH 8) | Storage Stability (25°C, sealed, 12 months) |
|---|---|---|---|---|---|
| Benzothiazol-2-yl thioester | 0.12 | Filtration, phase cut | 93–96% | ≤0.2% | Assay ≥98.5%; no agglomeration |
| 4-Nitrophenyl ester | 3.6 | Multiple alkaline washes | 85–90% | 1.0–1.8% | Partial hydrolysis to free acid, <1% |
| N-Hydroxysuccinimide ester | >50 (1-hydroxypyrrolidine-2,5-dione) | Brine wash (3× volume) | 78–84% | 0.5–1.2% | Assay drop ~5%; moisture-sensitive |
| Mixed anhydride (with pivaloyl chloride) | N/A (volatile co-product) | Evaporation | 82–88% | 2.0–3.5% | N/A; generated in situ |
| 2-Thiopyridyl ester | 2.8 (pyridine-2-thione) | Acidic wash, charcoal filtration | 88–91% | 0.3–0.6% | Darkening on storage; —SH dimer formation |
The benzothiazol-2-yl thioester is unique among the five comparator chemistries in combining a crystalline solid isolation form (eliminating the cryogenic handling and immediate consumption demanded by in-situ mixed anhydrides) with a by-product of such limited aqueous mobility that a single filtration imparts ≤0.1% residual thiol in the organic phase. This eliminates an entire wash operation — a 200 L water-immiscible solvent volume per 50 kg scale — and its associated solvent recovery distillation, thereby reducing the cumulative process mass intensity (PMI) of the acylation block by 12–15% relative to the p-nitrophenyl route. When a cephalosporin manufacturer switches from the nitrophenyl ester to the benzothiazol-2-yl thioester, the reduction in aqueous waste load has been documented in an EPA 33/50 Program voluntary disclosure to average 1.8 tonnes less organic-carbon load to the plant biotreater per metric tonne of bulk cefotaxime sodium produced.
The crystalline difference is also a processing advantage over the hydroxysuccinimide ester, which is frequently a hygroscopic semi-solid that must be stored at −20°C and used within 72 h after opening. By contrast, MAEM-BT-99 grade material packed in double-layered aluminium foil bags with a 5 g silica-gel sachet demonstrates no measurable change in water content or assay when stored at 2–8°C for 24 months (ongoing ICH stability study data, zone II conditions). Heat-flow microcalorimetry scans (25–200°C, 5°C·min⁻¹ ramp) confirm a single sharp endotherm without pre-melt exothermic events, consistent with the absence of polymorphic transitions that could alter dissolution kinetics during the scale-up of the biphasic acylation.
In cephalosporin synthesis where the target nucleus is not 7-ACA but 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thio]methyl-3-cephem-4-carboxylic acid (7-ACT) or 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid (7-AMCA), the benzothiazol-2-yl thioester performs equivalently provided the biphasic ratio is adjusted to 4:1 dichloromethane:water for 7-ACT to compensate for the substrate’s lower solubility in the organic phase. Industrial campaigns confirm that MAEM-BT-99 can be applied at a molar excess of only 1.08 eq relative to the 7-amino nucleus — compared to 1.25–1.40 eq typical for the p-nitrophenyl ester — because thioester hydrolysis in the alkaline aqueous phase proceeds at a rate constant khyd = 0.004 min⁻¹ at pH 8.0 and 0°C, roughly 60% slower than the nitrophenyl analogue. This lower hydrolysis propensity directly translates into reduced side-chain acid waste, which otherwise demands chromatographic clearance from the final cephem sodium salt crystallisation mother liquor.
The material is not registered as a pharmaceutical starting material under 21 CFR 314.70 and is supplied as a regulated intermediate for further processing only; it does not carry a DMF or CEP listing but is manufactured under an ISO 9001:2015-certified quality management system with annual surveillance audits. Its procurement specification is intended to align with the analytical control expectations of ICH Q7 for external raw materials used in antibiotic active pharmaceutical ingredient manufacturing.
