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Vincristine Product Introduction

  1. الاسم الانجليزي: Vincristine
  1. مواصفة
    • نقاء: Vincristine sulfate ≥ 98% (HPLC); high – purity grade: ≥ 99% (HPLC)
    • الذوبانية: Soluble in water (as sulfate salt, approximately 10 mg/mL), ethanol; insoluble in non – polar solvents like chloroform
    • Appearance – related: Loss on drying ≤ 1.0%, heavy metals ≤ 10 ppm, residual solvents ≤ 0.5%
    • Particle Size: Standard powder ≤ 100 μm; micronized powder ≤ 5 μm for better dissolution in parenteral formulations
  1. مظهر
    • White to off – white crystalline powder (sulfate salt form), odorless
  1. رقم CAS：2068 – 78 – 2 (Vincristine sulfate); 57 – 22 – 7 (Vincristine base)
  1. مهلة: 7 – 10 Working Days
  1. طَرد
    • 1 mg/vial (sterile glass vial), sealed under nitrogen; 10 mg/aluminum foil – lined bag for research – grade products
  1. السوق الرئيسي: Global pharmaceutical market, especially in North America, Europe, and Asia, predominantly used in oncology treatment and biomedical research
  1. سيناريوهات التطبيق

Core Properties

  • Molecular Formula: C₄₇H₅₅N₅O₁₁ (Vincristine); C₄₇H₅₅N₅O₁₁·H₂SO₄ (Vincristine sulfate)
  • Chemical Structure: An indole – alkaloid derived from Catharanthus roseus (Madagascar periwinkle), featuring a complex dimeric structure with a unique arrangement of indole and vindoline moieties.
  • Key Features
    • Antimitotic Agent: Binds to tubulin subunits, inhibiting microtubule polymerization. This disrupts the formation of the mitotic spindle during cell division, leading to cell cycle arrest at the metaphase stage and subsequent apoptosis of rapidly dividing cells.
    • High Selectivity for Neurons: While effective against cancer cells, it also has significant neurotoxicity due to its affinity for microtubules in neurons, affecting axonal transport and leading to peripheral neuropathy.
    • Low Bioavailability: Oral absorption is negligible, thus it is primarily administered intravenously for therapeutic use.
    • Potent Cytotoxicity: Even at low doses, it exhibits strong antitumor activity, but careful dosing is required to balance efficacy and minimize side effects.

سيناريوهات التطبيق

1. Oncology Treatment

  • Pediatric Cancers:
    • A crucial component in the treatment of acute lymphoblastic leukemia (ALL) in children, often used in combination regimens like VDLP (vincristine, daunorubicin, L – asparaginase, prednisone). It significantly improves remission rates, with cure rates for pediatric ALL exceeding 80% in many cases.
  • Adult Hematological Malignancies:
    • Used in the treatment of Hodgkin’s lymphoma and non – Hodgkin’s lymphoma, commonly included in combination chemotherapy protocols such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for non – Hodgkin’s lymphoma, enhancing treatment efficacy.
  • Solid Tumors:
    • Applied as part of adjuvant or palliative therapy for solid tumors like neuroblastoma, rhabdomyosarcoma, and Wilms’ tumor, either alone or in combination with other chemotherapeutic agents to control tumor growth and improve patient prognosis.

2. Biomedical Research

  • Cell Biology Studies:
    • Serves as a valuable tool for studying microtubule – dependent cellular processes, including cell division, intracellular transport, and cell motility. By disrupting microtubule dynamics, researchers can observe the impact on various cellular functions and signaling pathways.
  • Drug Development:
    • Used as a reference compound for developing novel antimitotic drugs. Its structure and mechanism of action inspire the design of analogs with potentially improved therapeutic indices, reduced toxicity, and enhanced selectivity for cancer cells.
  • Neurotoxicity Research:
    • Investigated to understand the mechanisms of chemotherapy – induced peripheral neuropathy. Studying vincristine – induced neurotoxicity helps in developing strategies to prevent or mitigate this common and debilitating side effect of cancer treatment.

طرق الكشف

  • High – Performance Liquid Chromatography (HPLC):
    • Column: C18 (250 × 4.6 mm, 5 μm), Mobile Phase: Acetonitrile – 0.1% formic acid (gradient elution), Flow Rate: 1.0 mL/min, Detection Wavelength: 297 nm for quantification.
  • Liquid Chromatography – Mass Spectrometry (LC – MS):
    • Employed for identifying vincristine and its metabolites in biological samples with high sensitivity. It provides detailed information about the compound’s structure and enables accurate quantification even at trace levels.
  • UV – Visible Spectroscopy:
    • Utilized as a rapid screening method to estimate vincristine concentration based on its characteristic absorption peak at 297 nm, useful for initial quality control and batch analysis during manufacturing.

Source & Advantages

  • مصدر طبيعي: Initially isolated from the leaves and stems of Catharanthus roseus. Due to the low natural yield (about 0.0001 – 0.001% dry weight) and environmental concerns, semi – synthetic and synthetic production methods are now predominantly used to meet the global demand.
  • Therapeutic Importance: A cornerstone in cancer chemotherapy, especially for hematological malignancies and certain pediatric cancers, where it has significantly improved survival rates and patient outcomes.
  • Research Significance: Facilitates fundamental research in cell biology and oncology, driving advancements in understanding cancer mechanisms and the development of more effective cancer treatments.

Regulatory Compliance

  • US FDA: Approved as an antineoplastic drug, strictly regulated under the Federal Food, Drug, and Cosmetic Act. Stringent manufacturing, labeling, and safety standards are enforced to ensure the quality and efficacy of vincristine – based products.
  • EMA (European Medicines Agency): Licensed for use in oncology, with continuous pharmacovigilance programs in place to monitor adverse effects and ensure patient safety throughout the product lifecycle.
  • China NMPA: Registered for clinical use in cancer treatment, subject to Good Manufacturing Practice (GMP) requirements and regular quality inspections to comply with national pharmaceutical standards.
التصنيفات: ,

Vincristine Sulfate: The Microtubule-Targeting Chemotherapy Agent Revolutionizing Oncology

1. What is Vincristine?

Vincristine sulfate is a dimeric Catharanthus alkaloid derived from the Madagascar periwinkle (Catharanthus roseus). As a microtubule-disrupting agent, it binds with high affinity to β-tubulin at the vinca domain, inhibiting microtubule polymerization and disrupting mitotic spindle assembly. This triggers metaphase arrest و apoptosis in rapidly dividing cells. Classified as a WHO Essential Medicine, it’s clinically indispensable for treating acute leukemias, lymphomas, and solid tumors through its potent antimitotic activity.

2. Source, Chemical Properties & Identifiers

  • مصدر: Isolated from Catharanthus roseus leaves; semi-synthesized from precursors catharanthine and vindoline

  • الخصائص الكيميائية:

    • Chemical Name: Methyl (2β,3β,4β,5α,12β,19α)-15-[(5S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indol-9-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate sulfate

    • Molecular Formula: C₄₆H₅₆N₄O₁₀·H₂SO₄

    • Molecular Weight: 923.04 g/mol

    • مظهر: White to off-white hygroscopic powder

    • الذوبان: Freely soluble in water (30 mg/mL), sparingly soluble in ethanol

    • Stability: Light-sensitive; degrades above pH 5.5

  • Key Identifiers:

    • CAS: 2068-78-2 (vincristine sulfate)

    • EC Number (EINECS): 218-216-0

    • MF: C₄₆H₅₈N₄O₁₄S

    • MW: 923.04

3. Pharmaceutical-Grade Specifications & Clinical Profile

  • Optimal Product: Requires >99.5% HPLC purity, <0.1% vinblastine (toxic analog), and endotoxin-free (<0.25 EU/mg). Shaanxi Zhonghong achieves this through countercurrent chromatography و lyophilization stabilization.

  • Therapeutic Applications:

    • Oncology: First-line for ALL (induction therapy), Hodgkin/non-Hodgkin lymphoma, neuroblastoma, Wilm’s tumor

    • الآلية: Binds tubulin dimer (Kd=85 nM) → suppresses microtubule dynamics → mitotic catastrophe

    • (Note: Nattokinase demonstrates fibrinolytic activity; no clinical evidence supports nephroprotective benefits)

  • Dosage:

    • IV Administration Only: 1.4-2.0 mg/m² weekly (max 2 mg/dose)

    • No oral bioavailability; never self-administer

  • Critical Safety Profile:

    • Neurotoxicity: Dose-limiting peripheral neuropathy (sensory > motor)

    • Hematologic: Mild myelosuppression (unlike vinblastine)

    • Autonomic Effects: Ileus, bladder atony, orthostatic hypotension

    • Extravasation Risk: Severe tissue necrosis requiring central line

    • موانع الاستعمال: Charcot-Marie-Tooth disease, intrathecal administration (fatal)

4. Shaanxi Zhonghong: cGMP Vinca Alkaloid Specialist
With 28+ years in plant-derived oncology APIs, we produce EP/USP-compliant vincristine sulfate:

  • Scientific Infrastructure:

    • 5 University Joint Labs (Tubulin binding research)

    • Patented Tech: CN202310XXXXXX (Vindoline stabilization)

  • Analytical Capabilities:

    • UPLC-MS/MS (purity/impurities)

    • 600MHz NMR (structural confirmation)

    • ICP-MS (elemental impurities)

    • LAL Chromogenic (endotoxins)

  • Global Distribution: API shipments to 80+ countries with cold-chain compliance

5. Pharmaceutical Quality Specifications

فئة المعلمة مواصفة Method
المبيدات الحشرية الكلوربيريفوس ≤0.01 mg/kg كروماتوغرافيا الغاز-مطياف الكتلة/مطياف الكتلة
Dimethoate ≤0.02 mg/kg LC-MS/MS
المعادن الثقيلة Pb ≤1.0 ppm ICP-MS (USP <232>)
Cd ≤0.5 ppm ICP-MS
علم الأحياء الدقيقة TAMC ≤10² CFU/g جامعة ساو باولو <61>
الإشريكية القولونية Absent/10g جامعة ساو باولو <62>
Critical Attributes Vincristine Sulfate ≥99.5% HPLC-PDA (USP <621>)
فينبلاستين ≤0.1% UPLC-MS
Water Content ≤4.0% Karl Fischer
Endotoxins <0.25 EU/mg LAL (USP <85>)

6. cGMP Manufacturing Process

  1. Botanical Sourcing: C. roseus cultivated under GACP guidelines

  2. Alkaloid Extraction: Ethanol/water gradient extraction (pH 4.0)

  3. Precursor Isolation: Ion-exchange chromatography (vindoline)

  4. Oxidative Coupling: Fe³⁺/H₂O₂-mediated dimerization

  5. Sulfation: Reaction with SO₃-pyridine complex

  6. بلورة: Controlled polymorph formation (Form II crystals)

  7. التجميد بالتجميد: -50°C freeze-drying under nitrogen atmosphere

  8. Sterile Filtration: 0.22 µm membrane filtration

7. Clinical & Research Applications

  • Oncology Protocols:

    • R-CHOP (lymphoma)

    • VDCLP (pediatric ALL)

  • Drug Delivery Systems:

    • Liposomal encapsulation (Marqibo®)

    • Peptide-drug conjugates (tumor-targeted delivery)

  • Neuroscience Research:

    • Axonal transport studies

    • Neurotoxicity modeling

8. cGMP Quality Control Protocol
Zhonghong’s 360° QC includes:

  • Identity: ¹³C NMR (C-18/C-19 carbonyl resonance at 175.2 ppm)

  • Purity: HPLC-ELSD quantifies vincristine (≥99.5%) and vinblastine (≤0.1%)

  • Potency: Tubulin polymerization assay (IC₅₀ 0.1-0.3 μM)

  • Safety: Bacterial endotoxins (kinetic chromogenic LAL), sterility testing (USP <71>)

  • Stability: 24-month shelf-life at 2-8°C (ICH Q1A validated)

9. Cold-Chain Packaging & Logistics

  • Primary Container: Type I amber vials (nitrogen headspace)

  • التغليف الثانوي: Vacuum-sealed Alu-PET pouches with desiccant

  • تخزين: 2-8°C protected from light

  • Shipping: Global cold-chain transport (2-8°C) via DHL Thermonet

10. Mechanism & Innovations

  • Molecular Action:

    • High-affinity binding to βIII-tubulin isotype

    • Suppresses microtubule dynamic instability by 95%

    • Induces Bim-mediated apoptosis

  • Zhonghong Innovations:

    • Enzymatic dimerization (yield ↑35%)

    • Cryogenic milling for particle size control

  • Research Frontiers:

    • Tubulin isotype-specific analogs

    • Neuroprotective co-administration (glutamate antagonists)

  • التحديات:

    • Neurotoxicity management

    • ABC transporter-mediated resistance

11. FAQ

Q1: Can vincristine be used as a dietary supplement?
A: Absolutely not. Vincristine is a cytotoxic chemotherapy agent requiring medical supervision. Unauthorized use causes severe neurotoxicity.

Q2: Does nattokinase benefit kidney patients?
*A: No clinical evidence supports nattokinase for kidney disease. Vincristine requires dose adjustment in renal impairment (CrCl <30 mL/min).*

Q3: Why is vinblastine impurity controlled?
*A: Vinblastine causes distinct myelotoxicity. Our UPLC-MS detects ≤0.05% impurity (ICH Q3A limits).*

Q4: What distinguishes Zhonghong’s vincristine?
*A: cGMP manufacturing, ≥99.5% purity, endotoxin control (<0.25 EU/mg), and patented lyophilization technology.*

Q5: Do you supply vincristine for ADCs?
*A: Yes. GMP-grade maleimide-activated vincristine available for antibody-drug conjugates (DAR 4-8).*

12. Global Procurement
Source cGMP vincristine sulfate:
✉️ بريد إلكتروني: liaodaohai@gmail.com
🌐 Web: www.aiherba.com
Request: COA, DMF, regulatory support, and custom synthesis options.

13. Conclusion
Vincristine sulfate remains a cornerstone of pediatric and hematologic oncology with unique microtubule-targeting properties. Its clinical utility depends on ultra-high purity (>99.5%), stringent neurotoxic impurity control، و temperature-managed distribution. Shaanxi Zhonghong combines three decades of vinca alkaloid expertise, patented stabilization technology، و cGMP compliance to deliver APIs meeting global pharmacopeial standards. Partner with us for uncompromising quality in cancer therapeutics.

14. References

  1. Noble RL, et al. (1958). J Am Chem Soc. 80:3487. [DOI:10.1021/ja01546a092]

  2. Jordan MA, et al. (1985). J Biol Chem. 260:14608. [PMID:2995464]

  3. WHO EML (2023): Vincristine sulfate injection

  4. USP Monograph: Vincristine Sulfate. USP44-NF39

  5. EMA Guideline CPMP/QWP/1850/04

  6. Lobert S, et al. (1996). Biochemistry. 35:6806. [DOI:10.1021/bi952483n]

  7. Zhonghong Patent: CN202310XXXXXX (Cryo-milling process)

  8. ICH Q3D (R2): Elemental Impurities

  9. FDA Label: Vincristine Sulfate Injection

  10. Gidding CEM, et al. (1999). Cancer Chemother Pharmacol. 44:266. [DOI:10.1007/s002800050976]

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