Cytarabine-5,6-d₂ | CAS No.: 40632-26-6
Chemical Name: Cytarabine-5,6-d₂
Molecular Formula: C₉H₁₁D₂N₃O₅
Molecular Weight: 245.23 g/mol
Isotopic Labeling: Deuterium (D₂) at the 5 and 6 positions of the cytosine ring
Purity: ≥ 98% (isotopic and chemical purity confirmed by LC-MS and NMR)
Product Overview
Cytarabine-5,6-d₂ is a stable isotope-labeled analog of Cytarabine (also known as Ara-C)—a pyrimidine nucleoside analog widely used as a chemotherapeutic agent in the treatment of various hematological malignancies, including acute myeloid leukemia (AML) and lymphomas. In this isotopically labeled compound, two hydrogen atoms on the cytosine ring (positions 5 and 6) are replaced with deuterium atoms (D₂), creating a mass shift that makes it exceptionally useful as an internal standard for LC-MS/MS quantification and metabolic tracing of Cytarabine and its metabolites.
At ResolveMass Laboratories Inc., we specialize in high-purity deuterated standards designed for bioanalytical method validation, pharmacokinetic studies, and isotope dilution mass spectrometry (IDMS). Cytarabine-5,6-d₂ is one of our key reference materials supporting the research and development of nucleoside-based therapeutics.
Chemical and Structural Information
Cytarabine (1-β-D-arabinofuranosylcytosine) is a synthetic analog of the naturally occurring nucleoside cytidine, in which the ribose sugar is replaced by D-arabinose. This structural modification allows Cytarabine to be incorporated into DNA during replication, where it inhibits DNA polymerase, ultimately leading to cell cycle arrest and apoptosis.
In Cytarabine-5,6-d₂, the substitution of hydrogen atoms with deuterium on the cytosine base does not alter its biological or chemical reactivity but provides a stable isotopic label that shifts its molecular mass by +2 Da. This small but significant mass difference enables researchers to accurately differentiate Cytarabine-5,6-d₂ from its unlabeled counterpart using high-resolution mass spectrometry. The deuteration also offers improved analytical stability and eliminates isotopic overlap during quantification.
Applications
1. Internal Standard for LC-MS/MS Quantification
Cytarabine-5,6-d₂ is widely employed as an internal standard in quantitative analytical assays to measure Cytarabine and its metabolites (e.g., Ara-UMP, Ara-UDP, Ara-CTP) in biological matrices such as plasma, serum, or cell lysates.
Using Cytarabine-5,6-d₂ provides:
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Accurate calibration for Cytarabine quantification
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Correction for ion suppression and matrix effects
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Enhanced reproducibility in pharmacokinetic and bioanalytical studies
Its identical chemical properties and retention time to Cytarabine make it an ideal internal standard for isotope dilution LC-MS/MS.
2. Pharmacokinetic and Metabolism Studies
Cytarabine-5,6-d₂ is a powerful tracer compound for investigating the absorption, distribution, metabolism, and excretion (ADME) of Cytarabine. Researchers use it to:
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Track metabolic conversion to Ara-CMP, Ara-CDP, and Ara-CTP
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Study enzymatic activation and deamination pathways
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Evaluate drug stability and clearance in preclinical and clinical samples
These studies are crucial for optimizing Cytarabine dosing regimens and understanding variability in patient responses.
3. Quality Control and Method Validation
Analytical and pharmaceutical laboratories use Cytarabine-5,6-d₂ as a reference standard during:
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Method development and validation for LC-MS or GC-MS assays
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Recovery and matrix effect assessments
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System suitability testing for mass spectrometric instruments
Its isotopic stability ensures consistent analytical performance, even under stringent chromatographic and sample preparation conditions.
4. Stable Isotope Tracer in Metabolomics
In advanced metabolomics and nucleoside flux studies, Cytarabine-5,6-d₂ enables precise tracking of labeled cytidine analog incorporation into nucleic acids. It is often used alongside other deuterated or ¹³C-labeled nucleosides to map nucleotide synthesis pathways and evaluate drug-nucleoside interactions at the molecular level.
Analytical Characterization
Each batch of Cytarabine-5,6-d₂ undergoes comprehensive analytical testing to confirm isotopic purity, structural integrity, and chemical stability.
Typical characterization methods include:
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¹H NMR and ²H NMR Spectroscopy – to confirm deuterium substitution at the 5 and 6 positions of the cytosine ring.
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High-Resolution LC-MS – for molecular weight verification and isotopic distribution analysis.
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HPLC Purity Analysis – confirming >98% purity for quantitative applications.
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FTIR Spectroscopy and Elemental Analysis – for identity verification.
A Certificate of Analysis (CoA) accompanies every batch, providing detailed isotopic labeling data and chromatographic purity results.
Advantages of Cytarabine-5,6-d₂
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Precisely deuterated at cytosine 5,6 positions (stable D₂ labeling)
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Chemically identical to native Cytarabine for ideal co-elution
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Enhances accuracy in LC-MS/MS quantification
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Minimizes variability due to matrix effects or ion suppression
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Excellent isotopic stability under typical storage and assay conditions
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Supports regulatory-compliant analytical and bioanalytical workflows
Safety and Handling
Cytarabine-5,6-d₂ should be handled with standard laboratory precautions. While it is not pharmacologically active at analytical concentrations, Cytarabine derivatives can be cytotoxic. Use gloves, protective eyewear, and appropriate containment. Dispose of waste in accordance with institutional and environmental regulations.
About ResolveMass Laboratories Inc.
ResolveMass Laboratories Inc. is a Canadian Contract Research Organization (CRO) specializing in stable isotope-labeled standards, impurity synthesis, and advanced analytical testing services. Our expertise supports global pharmaceutical, biotechnological, and academic research initiatives by delivering high-quality labeled reference materials for LC-MS, GC-MS, and metabolomic applications.
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