Nitazoxanide-d4 , CAS No.1246819-17-9

CAS: 1246819-17-9 Cat. No.: N646992 Formule: C₁₂H₅D₄N₃O₅S Poids moléculaire: 311.31

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Vue d’ensemble

Nitazoxanide-d 4 is the deuterium labeled Nitazoxanide, which is an antiprotozoal agent.

Form:Solid

Spécifications

Mécanismes biochimiques et physiologiques

Nitazoxanide-d 4 is the deuterium labeled Nitazoxanide, which is an antiprotozoal agent.

Conditions de stockage de stockage

Store at -20°C

Expédié en

Ice chest + Ice pads

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Type d'action

INHIBITOR

Noms et identifiants

Sourires canoniques

CC(=O)OC1=CC=CC=C1C(=O)NC2=NC=C(S2)[N+](=O)[O-]

IUPAC Name

[2,3,4,5-tetradeuterio-6-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl] acetate

InChIKey

YQNQNVDNTFHQSW-QFFDRWTDSA-N

INCHI

1S/C12H9N3O5S/c1-7(16)20-9-5-3-2-4-8(9)11(17)14-12-13-6-10(21-12)15(18)19/h2-6H,1H3,(H,13,14,17)/i2D,3D,4D,5D

Poids moléculaire

311.31

Reaxy-Rn

1225475

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=1225475&ln=

Propriétés chimiques et physiques

• Poids moléculaire: 311.310 g/mol
• XLogP3: 2.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 311.051 Da
• Monoisotopic Mass: 311.051 Da
• Topological Polar Surface Area: 142.000 Ų
• Heavy Atom Count: 21
• Formal Charge: 0
• Complexity: 428.000
• Isotope Atom Count: 4
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

• Example workflow for LC–MS/MS quantitation (research use only; adapt to your method)

  1. Stock preparation: Dissolve the compound in dry DMSO (e.g., 1–10 mg/mL). Prepare intermediate dilutions in MeOH or ACN as needed for spiking solutions. Filter through 0.2 µm PTFE if particulate is present.
  2. Calibration standards: Prepare matrix‑matched standards by spiking blank matrix with analyte and a fixed concentration of the d4 internal standard. Include low, mid, and high QC levels.
  3. Sample preparation: Spike internal standard into biological samples before protein precipitation (3–4 volumes of cold ACN or MeOH). Vortex, incubate on ice, centrifuge, and transfer supernatant.
  4. Mobile phase: Use volatile aqueous buffer (e.g., 0.1% formic acid or ammonium formate) with MeOH or ACN. Optimize for retention and ionization while maintaining ester stability (avoid high pH).
  5. Injection and analysis: Minimize autosampler residence time at ambient temperature; keep samples cooled. Verify co‑elution of analyte and internal standard and assess matrix effects via post‑column infusion or post‑extraction spiking.
  6. Data processing: Use isotope‑dilution calculations to derive concentrations; evaluate linearity, precision, accuracy, recovery, and stability per method validation guidance.

• Notes on isotope integrity

  • Confirm that your sample prep and LC–MS conditions do not induce H/D back‑exchange at labeled positions by stress‑testing and monitoring isotopologue distribution.

Biological Roles

• Context (general, literature for the unlabeled parent scaffold)

  • The nitazoxanide scaffold is biotransformed via ester hydrolysis to the corresponding phenolic amide (often termed tizoxanide). Subsequent phase‑II conjugation (e.g., glucuronidation) of the phenol is common in biological systems.
  • The d4 label enables tracing of absorption, distribution, metabolism, and excretion (ADME) pathways by mass spectrometry without altering the compound’s intrinsic reactivity profile.

• Research utility of the d4 analog

  • Internal standard for quantifying parent and metabolite concentrations in in vitro microsomal/S9 incubations and in vivo sample sets (research use only).
  • Supports studies of enzyme kinetics for esterases and conjugating enzymes by allowing isotope‑corrected quantitation.

• Important caveats

  • Isotopic substitution (D for H) is not expected to change biological binding qualitatively, but kinetic isotope effects may slightly alter reaction rates if deuterium is placed at a bond broken in the rate‑limiting step; design experiments accordingly.
  • Avoid over‑interpretation of small shifts in retention time or fragmentation patterns; verify co‑elution and product‑ion spectra.

No medical or clinical claims are made; this product is for laboratory research and analytical method development only.

Buffer Applications

This product is not a buffering agent and is not typically used to prepare biochemical buffer systems.

• Practical note
  • When used in LC–MS workflows, it is commonly diluted into volatile mobile phases (e.g., water/MeOH or water/ACN with 0.1% formic acid, ammonium acetate/formate). Choose mildly acidic conditions to balance ionization efficiency with ester stability.
  • For enzymology assays (e.g., esterase activity), use neutral buffers (phosphate, HEPES) and include organic co‑solvent at minimal fractions needed for solubilization; verify that buffer conditions do not induce ester hydrolysis independent of the intended enzymatic pathway.

Green Alternatives

While the compound itself is fixed, greener choices can be made in analytical workflows.

• Solvent selection for LC–MS and sample prep (general comparison)

  • MeOH vs ACN: MeOH is generally considered greener (renewable sources, lower toxicity), though ACN can offer sharper peaks in some methods. Where feasible, optimize for MeOH‑rich mobile phases without compromising data quality.
  • EtOH as an alternative to MeOH for some extractions can reduce toxicity; verify recovery and stability.
  • Buffering: Use volatile, low‑toxicity modifiers (e.g., formic acid, ammonium formate/acetate) at the lowest effective concentration.

• Waste minimization

  • Employ microflow LC or reduced‑volume sample prep to cut solvent consumption.
  • Consolidate washes and use multi‑use rinse streams where contamination risk is controlled.

• Energy and storage

  • Store at −20°C as specified; minimize freeze–thaw cycles by aliquoting to reduce waste from degraded material.

Tradeoffs: Greener solvents may slightly alter retention/ionization; validate method performance (sensitivity, peak shape, carryover) when substituting ACN with alcohols.

Pharmaceutical Uses

• Role in pharmaceutical research and development (no therapeutic claims)

  • Employed as a stable‑isotope internal standard in bioanalytical method development and validation (e.g., GLP studies) for quantifying the parent scaffold and its metabolites in preclinical samples.
  • Useful in recovery experiments, matrix effect assessments, and stability studies (autosampler stability, freeze–thaw) as part of method validation protocols (e.g., following FDA/EMA bioanalytical guidance).

• Excipients/compendial status

  • No pharmacopeial monograph or excipient role is indicated for this deuterated compound. Any compendial status would pertain to the unlabeled parent if applicable; consult regulatory references as needed.

• Manufacturing context

  • Stable‑isotope standards support process analytical technology (PAT) and QC release testing of dosage forms containing the unlabeled parent by providing traceable, isotope‑dilution calibration standards.

This product is for research use only and is not for human or veterinary use.

Physical Properties

• Item-specific values (specification-grade):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight (item): Not specified for this item; refer to CoA/Spec Sheet.
  • Other specs (water/peroxides/metals/UV cutoff): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/typical information for the unlabeled parent (nitazoxanide) — for context only, not product specifications

  • Physical state: crystalline solid (literature).
  • Aqueous solubility: low; more soluble in polar organic solvents such as DMSO, DMF, and alcohols (literature).
  • Chemical stability: the acetate ester can hydrolyze in basic or strongly nucleophilic aqueous media; the amide is more robust; nitrothiazole ring can be reduced under strongly reducing conditions (literature).

• Practical handling implications (general)

  • Prepare analytical stock solutions in dry DMSO, MeOH, or ACN for LC–MS use; dilute into aqueous buffers immediately before analysis to minimize ester hydrolysis.
  • Avoid prolonged exposure to high pH or strong nucleophiles if unintentional deacetylation is a concern.

Note: Exact numerical values (mp, bp, density, logP, pKa, refractive index) are not provided for this specific d4 item and should be taken from the CoA/Spec Sheet if required.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance for stable‑isotope–labeled small molecules used in LC–MS

  • Typical expectations include high chemical purity and high isotopic enrichment, with tight control of unlabeled/isotopologue impurities to prevent quantitation bias in isotope‑dilution assays.
  • If an internal standard is intended for bioanalytical methods, low levels of residual solvents and well-characterized isotopic distribution are important. Certificates typically provide enrichment (e.g., ≥98 atom % D at defined sites) and LC–MS purity.

• Stabilizers/impurities

  • No stabilizers are listed in the Product Data. If stabilizers or counterions are present, they will be disclosed on the CoA.

• How to use CoA information effectively

  • Verify isotopic labeling pattern, enrichment, and chemical purity before constructing calibration curves.
  • Match the internal standard’s retention and fragmentation behavior to the analyte (parent nitazoxanide or its metabolite) to ensure accurate correction for matrix effects.

Reaction and Applications

• Primary application domain (research use only)

  • Stable‑isotope internal standard for quantitative LC–MS/MS of nitazoxanide and related analytes in complex matrices (plasma, tissue homogenates, environmental extracts). Supports isotope‑dilution accuracy and correction for matrix effects.

• Metabolism/biotransformation studies (general, literature)

  • The parent scaffold is known to undergo ester hydrolysis to the deacetylated phenolic amide (commonly referred to as tizoxanide). The d4 analog enables tracing of hydrolysis and conjugation pathways (e.g., glucuronidation of the phenol) by mass shift without altering chemistry.

• Sample preparation tips

  • Spike the d4 internal standard early (pre‑extraction) to compensate for losses and matrix suppression.
  • Protein precipitation with ACN or MeOH is commonly effective; ensure rapid processing at low temperature and neutral pH to limit ester cleavage.
  • Validate absence of H/D back‑exchange at labeled sites under your prep and LC–MS conditions; avoid strong acids/bases or catalysts that accelerate exchange if labels are at labile positions.

• Calibration/quantitation

  • Construct matrix‑matched calibration curves using constant internal‑standard concentration across levels.
  • Monitor both parent and known metabolites if the analytical scope includes biotransformation; ensure the internal standard co‑elutes sufficiently to track matrix effects.

• Not typically used as a synthetic reagent; its utility is predominantly analytical.

Reaction Conditions

The compound is primarily used as an analytical standard. If chemical transformations are part of method development or mechanistic studies, the following general, literature‑based conditions apply to the scaffold (not product specifications):

• Ester hydrolysis (to the phenolic amide)

  • Base‑catalyzed: Aqueous NaOH or K2CO3 in MeOH/H2O or ACN/H2O at ambient to mild heat can effect deacetylation; monitor by LC–MS to avoid overreaction.
  • Enzymatic: Carboxylesterases in neutral buffers (pH ~7–7.5) at 37°C are commonly used for in vitro hydrolysis assays.

• Stability considerations

  • Avoid strong reducing conditions (e.g., catalytic hydrogenation, dithionite) that could reduce the nitro group on thiazole.
  • Maintain mildly acidic to neutral pH during analytical handling to limit non‑enzymatic ester cleavage.

• LC–MS handling

  • Prepare stock in DMSO/MeOH; dilute into mobile phase just prior to injection. Keep autosampler at low temperature (e.g., 4–10°C) to enhance stability during runs.

Note: Specific temperatures, times, and yields depend on experimental setup; verify by small‑scale trials. If isotope placement is at potentially labile positions, confirm absence of H/D back‑exchange under chosen conditions.

Safety and Handling

• GHS classification and hazard statements

  • Signal Word: Not specified for this item; refer to SDS.
  • H‑Statements: Not specified for this item; refer to SDS.
  • GHS Classification/Pictograms: Not specified for this item; refer to SDS.

• General laboratory precautions (good practice for nitro-heteroaromatic amide esters)

  • Use in a chemical fume hood; avoid inhalation of dust/aerosols.
  • Wear appropriate PPE: lab coat, safety glasses, and chemically resistant gloves (nitrile recommended). For weighing fine powders, consider a dust mask/respirator as per SDS guidance.
  • Avoid contact with strong bases, strong acids, and strong reducing agents that may promote ester cleavage or nitro reduction.

• First aid overview (consult SDS for full guidance)

  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical advice if irritation continues.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

• Special risks/considerations

  • Deuterated compounds are handled as their unlabeled analogs from a hazard perspective; isotopic substitution does not imply reduced hazard.
  • For LC–MS sample prep, minimize exposure to light/heat and maintain neutral pH to limit ester hydrolysis.

Always defer to the product-specific SDS for authoritative safety information.

Solvent Selection

This compound is a neutral, moderately lipophilic nitrothiazolyl amide-ester scaffold; aqueous solubility is limited (literature for the unlabeled parent). Solvent choice is primarily driven by analytical or preparative use.

• Stock solution preparation (analytical)

  • Recommended: dry DMSO for concentrated stocks; MeOH or ACN for LC–MS calibration standards.
  • Working dilutions: Prepare in aqueous mobile phase immediately before injection to limit ester hydrolysis; include 0.1% formic acid or a volatile buffer if required for ionization, balancing hydrolytic stability.

• Miscibility/polarity considerations (general)

  • Polar aprotic solvents (DMSO, DMF, ACN) solubilize well; alcohols (MeOH, EtOH) are often adequate. Water requires co‑solvent.
  • Avoid strong basic aqueous media that accelerate deacetylation to the corresponding phenolate/carboxylate.

• Comparison notes (general)

  • DMSO: maximum solubilization, but high viscosity and potential ion suppression in ESI if not diluted adequately.
  • MeOH: good LC–MS compatibility and greener than ACN; can promote transesterification under strongly basic conditions.
  • ACN: excellent LC–MS volatility; less green; may offer sharper peaks for some methods.

Choose the solvent system based on downstream application and stability constraints; verify by a small‑scale solubility/stability check.

Storage and Reconstitution

• Storage conditions (from Product Data)

  • Store at −20°C.
  • Shipped in ice chest with ice pads.

• Handling and aliquoting

  • Allow container to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation.
  • Prepare single‑use aliquots of solid or concentrated stock solution to minimize freeze–thaw cycles.

• Reconstitution/stock preparation

  • Recommended solvents: dry DMSO for concentrated stocks; MeOH or ACN for working solutions compatible with LC–MS.
  • Vortex until fully dissolved; if needed, brief sonication can assist dissolution. Record final concentration and solvent.
  • Store solutions at −20°C protected from light; verify stability over intended storage by periodic LC–MS checks.

• Stability cautions (general)

  • Avoid prolonged exposure to high pH or elevated temperatures that can promote ester hydrolysis.
  • If isotopic labels could be exchangeable under harsh conditions, avoid strong acids/bases and heterogeneous catalysts during handling.

For any item‑specific stability data (solution stability, recommended shelf life), consult the CoA/Spec Sheet.

Structure and Identity

A stable‑isotope–labeled analog of nitazoxanide, intended for analytical and research applications (isotope dilution LC–MS/MS, metabolism studies).

• Item-specific identifiers (from Product Data)

  • CAS: 1246819-17-9
  • PubChem CID: 71751033
  • InChIKey: 444275 (as provided; abbreviated/not standard-length)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general chemistry knowledge for nitazoxanide scaffold; deuteration pattern not specified)

  • Core scaffold: an amide linking a substituted salicylate/phenyl ester to a 5‑nitrothiazole ring.
  • Functional groups: aromatic ester (acetoxy on an o‑hydroxybenzamide framework), primary amide, nitro group on thiazole, thiazole heteroaromatic.
  • Isotopic label: four deuterium atoms (d4). Exact labeling sites are not specified in the Product Data; consult the CoA/Spectrum for positioning.

• 2D description in words (general)

  • A phenyl ring bearing an ortho acyloxyl substituent and an amide at the adjacent position, with the amide nitrogen bound to a 5‑nitrothiazolyl ring. The d4 variant maintains the same connectivity as the unlabeled parent; the C–D bonds replace selected C–H positions without altering functional groups or formal charge.

Synthetic Utility

This compound is not commonly used as a general synthetic building block; its primary value lies in analytical chemistry. Nonetheless, understanding functional group reactivity aids in handling and derivatization studies.

• Functional group reactivity (general for the scaffold)

  • Aromatic ester: susceptible to base‑catalyzed hydrolysis and transesterification; acid‑catalyzed hydrolysis possible but slower under mild conditions.
  • Amide: comparatively stable; requires strong activation or forcing conditions for hydrolysis.
  • Nitrothiazole: reducible under hydrogenation or with single‑electron donors; conditions should be avoided when label integrity of the parent scaffold is needed.

• Isotope integrity

  • If the deuterium atoms reside at potentially exchangeable benzylic/aryl positions under acidic/basic catalysis, harsh conditions can cause H/D exchange. Validate label stability under any derivatization or forced‑degradation studies.

• Derivatization in analytics

  • Phenolic metabolite (after hydrolysis) can be derivatized (e.g., silylation for GC–MS) if needed; consider isotope effects on fragmentation and retention.

Overall, treat this as an analytical reference material rather than a precursor for multi‑step synthesis.

Target Specificity

Not applicable. This product is a small‑molecule stable‑isotope standard, not an antibody or targeted biologic. No antigen/epitope, clone, isotype, or species reactivity information applies.