Pioglitazone-d4 - ≥99% , CAS No.1134163-29-3

CAS: 1134163-29-3 Cat. No.: P646951 Formula: C₁₉H₁₆D₄N₂O₃S Molecular Weight: 360.46

GRADE & PURITY ≥99%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Pioglitazone-d 4 is a deuterium labeled Pioglitazone. Pioglitazone (U 72107) is a potent and selective PPARγ agonist with high affinity binding to the PPARγ ligand-binding domain with EC50 of 0.93 and 0.99 μM for human and mouse PPARγ , respectively.

Form:Solid

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

Pioglitazone-d 4 is a deuterium labeled Pioglitazone. Pioglitazone (U 72107) is a potent and selective PPARγ agonist with high affinity binding to the PPARγ ligand-binding domain with EC50 of 0.93 and 0.99 μM for human and mouse PPARγ , respectively.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

Molecular Weight

360.46

Application Protocols

No item-specific, validated protocols are provided in the Product Data. The following is general guidance for using deuterated internal standards in LC–MS assays.

Example: Plasma quantitation of pioglitazone (general)

• Internal standard stock: Dissolve Pioglitazone-d4 at 1 mg/mL in methanol. Store aliquots at −20 °C.
• Working IS solution: Dilute to 100 ng/mL in 50:50 ACN:water with 0.1% formic acid.
• Sample prep (protein precipitation): To 50 µL plasma, add 10 µL IS working solution, then 200 µL cold ACN (or MeOH). Vortex 1 min, centrifuge 10 min at 14,000 g. Transfer supernatant to an LC vial.
• LC–MS/MS: Inject 2–10 µL onto a C18 column. Mobile phase A: water + 0.1% formic acid; B: acetonitrile + 0.1% formic acid. Monitor MRM for analyte and IS (IS precursor typically +4 Da vs analyte). Quantify with a 1/x weighted calibration curve.
• QC: Include low/mid/high QC levels and evaluate accuracy (±15%) and precision (≤15% RSD) per bioanalytical guidelines.

Notes

• Adapt extraction (SPE, LLE) to your matrix. Verify absence of isotopic interference between d0 and d4 channels given the instrument’s resolution.
• All values above are illustrative and must be validated on your system.

Biological Roles

Item scope

• No biological activity or targets are specified for this deuterated standard in the Product Data; it is sold for research use only.

Literature context for the parent compound (pioglitazone)

• Molecular target: Pioglitazone is a ligand of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that regulates transcription of genes involved in glucose and lipid metabolism.
• Mechanistic notes: Binding to PPARγ influences adipocyte differentiation and lipid handling pathways (biochemistry context). These roles underpin its common use as a reference analyte in bioanalytical and metabolism studies.

Use of the deuterated analog

• Pioglitazone-d4 itself is not intended as a biological modulator but as an internal standard enabling accurate quantification of the parent compound in biological matrices (plasma, serum, tissues) and in in vitro systems (microsomes, hepatocytes).

Caveats

• Do not infer therapeutic or clinical performance from this material. Any discussion of biological pathways is provided solely to contextualize analytical applications.
• If your study examines receptor binding or downstream pathways, use the non-deuterated compound as the active analyte and apply the d4 analog strictly for quantitation and method control.

Buffer Applications

Not typically applicable. Pioglitazone-d4 is a small-molecule isotopic standard and is not used to formulate buffering systems.

Practical note (general)

• For LC–MS workflows, aqueous mobile phases or sample diluents may include volatile buffers (e.g., 0.1% formic acid or 5–10 mM ammonium formate/acetate) to aid ionization and chromatographic performance. The d4 standard should be compatible with these systems when dissolved initially in MeOH/ACN and then diluted with the buffered aqueous phase.
• Ensure pH and buffer choice do not induce analyte/IS degradation; evaluate stability in your intended matrix and storage conditions.

Green Alternatives

Scope: Green chemistry considerations here focus on solvent choices and analytical workflow design for handling pioglitazone-d4; the compound itself is fixed by analytical needs.

Greener choices (general guidance)

• Solvent selection in LC–MS sample prep:
  • Prefer ethanol or isopropanol for protein precipitation when possible instead of acetonitrile; evaluate recovery and matrix effects.
  • Use methanol in place of dichloromethane for LLE where compatible.
• Chromatography
  • Employ water-rich gradients and minimize acetonitrile consumption by optimizing column dimensions and particle size.
  • Consider supercritical CO2 (SFC) for certain separations to reduce organic solvent usage, recognizing method transfer complexity.
• Waste minimization
  • Prepare concentrated stock solutions to reduce solvent volume in dilutions.
  • Use 96-well microextraction formats to cut solvent use per sample.

Trade-offs

• ACN often provides superior protein precipitation and MS performance; greener alcohols may increase phospholipid carryover or ion suppression. Empirical evaluation is required.
• DMSO is not particularly green but enables high solubility and small-volume stocks, reducing total solvent consumption.

Summary

• While the isotopically labeled standard is dictated by analytical selectivity, substantial sustainability gains can come from judicious solvent choice, micro-scale workflows, and efficient chromatographic methods.

Pharmaceutical Uses

Scope: No excipient or pharmacopeial status is provided in the Product Data. This product is for research use only and is not for human or veterinary use.

Typical roles of deuterated standards in pharmaceutical R&D/QA (general)

• Bioanalytical quantitation: Internal standard for validated LC–MS/MS assays measuring pioglitazone in PK, ADME, or stability studies.
• Stability-indicating methods: Supports forced-degradation studies by correcting for matrix and ionization variability.
• Manufacturing analytics: Reference material for in-process control assays and release testing of drug substance/product (laboratory context only).

Documentation expectations

• For regulated work, obtain a full CoA detailing chemical purity, isotopic enrichment/profile, identity (HRMS), and residual solvents. If used as a working standard, maintain traceability and storage logs per your QA system.

Limitations

• This product is not a therapeutic agent, API, or excipient. Do not use for clinical diagnosis or treatment.

Physical Properties

Item-specific values

• Molecular weight, formula, melting point, solubility, logP, refractive index: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties for the non-deuterated parent (pioglitazone) for context only

• Physical form: typically a crystalline solid; sparingly soluble in water; soluble in polar aprotic organics (DMSO, DMF) and alcohols (MeOH, EtOH).
• Melting point: approximately 193–195 °C (literature, parent compound; deuteration usually has negligible effect on MP).
• LogP (octanol/water): reported around 2.3–3 (literature range, parent compound), indicating moderate lipophilicity.
• pKa: the TZD NH is weakly acidic (literature reports pKa ca. 6–7 for analogous TZDs; exact value depends on substitution).
• UV characteristics: aromatic rings and TZD carbonyls give useful absorbance in the near-UV; exact λmax depends on solvent (literature, parent compound).

Practical notes (general)

• Deuteration (+4 Da) minimally affects bulk physical properties but improves mass spectrometric selectivity. If your method relies on chromatographic co-elution, retention time for d4 is typically within seconds of the parent but can show slight isotope effects; verify with your method. Always consult the specific CoA for item-grade property data required for validated methods.

Quality & Grades

Item-specific grade/purity

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

What to expect for deuterated analytical standards (general guidance)

• Isotopic enrichment: Deuterated standards are typically specified by isotopic purity (e.g., %D and %d4 isotopomer distribution) and chemical purity (HPLC/GC area %). Because exact enrichment and isotopomer profile directly affect quantitation, consult the CoA for this lot’s data.
• Residual protio content: Minor d0–d3 species are often present; isotope-dilution LC–MS methods should account for observed isotopic composition via response factor calibration.
• Counterions and form: Confirm whether the product is the free base or a salt (e.g., HCl). For pioglitazone-related materials, both forms exist in commerce; form impacts solubility and exact molecular weight used for calculations.
• Trace impurities: Typical CoA data may include residual solvents and water (Karl Fischer). Since these are not specified here, verify on the supplied documentation if needed for regulated workflows.
• Suitability for purpose:
  • Bioanalytical LC–MS: Look for low UV background impurities, high chemical purity (≥98% typical), narrow isotopic distribution, and documented stability.
  • Reference standard use: Ensure identity verification via HRMS and NMR data supplied in the CoA.

Note: Where item-specific values are critical (purity %, d4 incorporation, residual solvents), rely on the CoA/Spec Sheet for this SKU.

Reaction & Applications

Primary application domain (general)

• Isotope-dilution mass spectrometry (IDMS): Pioglitazone-d4 serves as an internal standard to correct for matrix effects, recovery, and instrument variability in quantitative LC–MS/MS assays of pioglitazone in biological or environmental samples.
• Method development: Used to optimize extraction efficiency (protein precipitation, LLE, SPE) and to validate linearity, accuracy, precision, and stability-indicating conditions.

Analytical workflow notes (general)

• Co-elution: Aim for chromatographic co-elution of d4 with the analyte; verify that isotope effects do not materially shift retention under your gradient.
• MRM transitions: Select precursor m/z at [M+H]+ shifted by +4 Da relative to the parent; fragment ions may exhibit partial H/D scrambling depending on labeling positions. Optimize collision energies empirically.
• Matrix considerations: Spike the internal standard early (e.g., pre-extraction) to correct for losses. Evaluate ion suppression across the chromatographic window using post-column infusion.

Not typically used as a synthetic reagent

• Pioglitazone-d4 is not commonly used in preparative organic synthesis or as a coupling partner. For synthetic work on pioglitazone analogs, unlabeled intermediates or selectively deuterated building blocks are preferred.

Regulatory context

• For regulated bioanalysis, ensure full traceability of lot-specific isotopic purity, identity confirmation (HRMS/NMR), and stability per your validation protocol.

Reaction Conditions

Not typically a substrate for bench reactions in this context. This section provides general analytical handling conditions rather than synthetic reaction parameters.

General LC–MS handling conditions (literature/practice)

• Stock preparation: 0.5–10 mg/mL in MeOH, ACN, or DMSO. Filter through 0.2 µm PTFE if particulate is present.
• Working solutions: 1–1000 ng/mL achieved by serial dilution in 50:50 ACN:water with 0.1% formic acid or 5–10 mM ammonium formate. Include 0.1–1% organic modifier to mitigate adsorption.
• Ionization: Positive-mode ESI is commonly used for pioglitazone; optimize source conditions (capillary voltage, temperature, desolvation gas) empirically.
• Chromatography: C18 or phenyl-hexyl columns, 2–20 minute gradients with water/ACN (0.1% FA). Slight isotope effects on retention are possible but usually minor.
• Stability checks: Assess bench-top, autosampler (4–10 °C), freeze–thaw, and long-term freezer stability using QC levels bracketing expected concentrations.

Note

• These are general literature/practice guidelines for the parent compound’s analysis. Always validate conditions with your instrumentation and confirm compatibility with the deuterated standard supplied.

Safety & Handling

Hazard Information (item-specific)

• GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.

General laboratory safety guidance (consult SDS for definitive instructions)

• Handling: Work in a well-ventilated area or fume hood. Avoid inhalation of dust or aerosols and contact with skin/eyes. Use appropriate PPE: lab coat, safety glasses, and nitrile gloves.
• Weighing and transfers: As a micro-analytical standard, quantities are small. Use antistatic measures and closed containers to minimize airborne particulate. Consider pre-dissolving in a clean solvent (e.g., MeOH or ACN) for spiking solutions.
• Incompatibilities: Strong oxidizers and strong bases/acids may degrade thiazolidinedione/ether functionalities (general chemical principle). Avoid prolonged exposure to moisture and light.
• First aid (general): If inhaled, move to fresh air. In case of skin contact, wash with soap and water. If in eyes, rinse cautiously with water for several minutes. If ingested or upon any adverse exposure, seek medical attention. Provide the SDS to healthcare providers.
• Spill/leak: Avoid dust formation. Absorb small spills with inert material (silica, vermiculite) and dispose per institutional and local regulations.
• Waste: Dispose as organic laboratory waste according to your institution’s hazardous waste program.
• Note: This product is for research use only.

Solvent Selection

Applicability: As a moderately lipophilic small molecule, pioglitazone-d4 is commonly handled as a stock solution for LC–MS workflows rather than used as a bulk solvent or reagent.

General solvent guidance (literature, parent compound behavior)

• Preferred solvents for stock solutions: DMSO, methanol (MeOH), acetonitrile (ACN). These provide excellent solubility and are LC–MS compatible.
• Aqueous solubility: Low for the neutral form; aqueous buffers often require co-solvent or mild base to improve apparent solubility (verify compatibility with your assay).
• Polarity and miscibility context: DMSO (highly polar, fully miscible with water) offers robust dissolution; MeOH/ACN provide volatility desirable for LC–MS and easy evaporation.

Selection tips

• Calibration standards for LC–MS: Prepare concentrated stocks in MeOH or ACN and serially dilute with 50:50 ACN:water (0.1% formic acid optional) to minimize adsorption and maintain peak shape.
• Adsorptive losses: Reduce by using silanized glass or polypropylene, and include 0.1–1% DMSO in dilute working solutions to improve recovery.
• Salt form considerations: If the product is received as a salt, water or buffered mixtures may be more suitable; confirm form via CoA.

Comparison (general)

• DMSO: maximal solubility, non-volatile; best for master stocks.
• MeOH: volatile, MS-friendly, slightly protic; good for routine standards.
• ACN: volatile, MS-friendly, less protic; excellent for gradient LC but may require small water content to avoid adsorption.

Storage & Reconstitution

Item-specific storage and shipping

• Storage Conditions: Store at −20 °C (from Product Data).
• Shipped In: Ice chest + Ice pads (from Product Data).

General handling and reconstitution

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Initial dissolution: Prepare concentrated stocks in high-purity methanol, acetonitrile, or DMSO. Typical ranges: 0.5–10 mg/mL depending on downstream use. Vortex until fully dissolved; gentle warming (≤30 °C) may assist, avoiding prolonged heating.
• Aliquoting: Dispense into single-use, low-bind vials to minimize freeze–thaw cycles and adsorption losses.
• Storage of solutions: Store frozen (−20 °C) protected from light. For autosampler residence, keep at 4–10 °C and limit to ≤48 hours unless stability is verified.
• Freeze–thaw guidance: Avoid repeated cycling; thaw at room temperature, mix gently, and return unused portion promptly to −20 °C. Document the number of cycles used in validated assays.
• Light/moisture protection: Use amber vials and desiccants where possible to limit photodegradation and hydrolysis.

Stability notes

• Lot-specific stability (solid and solution) is not provided here; consult the CoA/SDS and perform in-matrix and neat-solution stability assessments aligned with your method validation requirements.

Research use

• For research use only.

Structure & Identity

Brief: Pioglitazone-d4 is the deuterium-labeled analog of pioglitazone, typically used as an isotopic internal standard for analytical assays.

• Item-specific identifiers (from Product Data)
  • CAS: 1134163-29-3
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • 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 (literature, parent compound pioglitazone)
  • Core scaffold: 1,3-thiazolidine-2,4-dione ring (thiazolidinedione, TZD) attached via a benzyl linker to a para-substituted phenyl ring bearing a 2-(pyridyl)ethyl ether substituent.
  • Functional groups: cyclic imide-like dione (acidic NH), thiazolidinyl sulfur, aromatic phenyl and pyridyl rings, aryl–O–alkyl ether, benzylic methylene.
  • Isotopic labeling: “d4” indicates four hydrogen atoms are replaced with deuterium (2H). Exact labeling positions can vary by supplier/batch; consult the CoA for labeling map.
• 2D structural description (literature)
  • A five-membered TZD ring bearing two carbonyls is linked at the 5-position to a benzylic methylene that connects to a para-phenyl ring. The para position carries an ethoxy linker to a 2-substituted pyridine ring. Deuteriums are typically installed on metabolically stable positions (e.g., aromatic/benzylic) to enhance MS discrimination, but exact sites must be confirmed from the item’s CoA.

Synthetic Utility

Direct synthetic use: Limited. Pioglitazone-d4 is generally not employed as a building block in synthesis due to cost and the objective of preserving known isotopic labeling for analytics.

Relevance to synthesis (general)

• Label placement: Deuterium incorporation can be achieved via H/D exchange at activated positions (e.g., benzylic, aromatic under catalytic conditions) or through use of deuterated intermediates during assembly of the TZD-aryl-ether scaffold. Understanding likely labeling sites helps predict MS/MS behavior and potential isotope loss during reactions or sample prep.
• Stability considerations: The thiazolidinedione N–H can undergo exchange in strongly basic D2O-containing systems; avoid conditions that could scramble deuterium if label integrity is critical to your study.

When synthetic modification is needed

• For metabolite synthesis or analog generation, start from unlabeled pioglitazone or labeled building blocks rather than from the final d4 standard to maintain precise isotope patterns and avoid dilution of label through transformations.

Analytical method development utility

• Use the d4 compound to benchmark extraction recoveries across different sample prep chemistries (SPE sorbents, LLE solvent systems) and to probe adsorption/carryover on various labware and column chemistries.

Target Specificity

Not applicable. This product is a small-molecule isotopic standard and not a biological macromolecule or targeting reagent. No antigen, epitope, clone, or species reactivity information applies.

Context (literature)

• The parent compound pioglitazone is known to bind PPARγ (biochemical target), but this deuterated standard is intended solely for analytical quantitation and does not denote biological targeting specificity.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥99% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1134163-29-3, the molecular formula is C19H16D4N2O3S, and the molecular weight is 360.46 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.