Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H15N2O3PS.3H2O |
Molecular Weight | 268.269 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.O.NCCCNCCSP(O)(O)=O
InChI
InChIKey=TXQPXJKRNHJWAX-UHFFFAOYSA-N
InChI=1S/C5H15N2O3PS.3H2O/c6-2-1-3-7-4-5-12-11(8,9)10;;;/h7H,1-6H2,(H2,8,9,10);3*1H2
Molecular Formula | C5H15N2O3PS |
Molecular Weight | 214.223 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | H2O |
Molecular Weight | 18.0153 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=17602063
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=17602063
Amifostine is an organic thiophosphate cytoprotective agent known chemically as 2-[(3¬ aminopropyl)amino]ethanethiol dihydrogen phosphate (ester), it’s adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed under the trade name Ethyol. Amifostine is a prodrug and is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of Ethyol to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumor cells.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
Curator's Comment: Because amifostine does not cross the blood–brain barrier, the central nervous system, often the dose-limiting organ in radiotherapy, is not protected
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10628381 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Secondary | ETHYOL Approved UseAmifostine for Injection is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. Amifostine for Injection is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands (see Clinical Studies ). For the approved indications, the clinical data do not suggest that the effectiveness of cisplatin based chemotherapy regimens or radiation therapy is altered by Amifostine for Injection. There are at present only limited data on the effects of amifostine on the efficacy of chemotherapy or radiotherapy in other settings. Amifostine should not be administered to patients in other settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy, except in the context of a clinical study (see WARNINGS). Launch Date1995 |
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Secondary | ETHYOL Approved UseAmifostine for Injection is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patient s with advanced ovarian cancer. Amifostine for Injection is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands (see Clinical Studies ). For the approved indications, the clinical data do not suggest that the effectiveness of cisplatin based chemotherapy regimens or radiation therapy is altered by Amifostine for Injection. There are at present only limited data on the effects of amifostine on the efficacy of chemotherapy or radiotherapy in other settings. Amifostine should not be administered to patients in other settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy, except in the context of a clinical study (see WARNINGS). Launch Date1995 |
Doses
Dose | Population | Adverse events |
---|---|---|
200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Nausea and vomiting, Nausea and vomiting... Other AEs: Nausea and vomiting (grade 3-4, 8%) Sources: Nausea and vomiting (all grades, 53%) Hypotension (grade 3-4, 3%) Hypotension (all grades, 15%) |
910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Blood pressure decreased... Other AEs: Nausea and vomiting, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Blood pressure decreased (<3%) Other AEs:Nausea and vomiting (grade 3-4, 30%) Sources: Nausea and vomiting (all grades, 96%) Hypotension (grade 3-4, 8%) Hypotension (all grades, 61%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | all grades, 15% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | all grades, 53% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | grade 3-4, 3% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | grade 3-4, 8% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Blood pressure decreased | <3% Disc. AE |
910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | all grades, 61% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | all grades, 96% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | grade 3-4, 30% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | grade 3-4, 8% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats. | 2000 |
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Systemic inflammatory response syndrome associated with amifostine. | 2000 Apr |
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Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study. | 2000 Aug |
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Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. | 2000 Aug |
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Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation. | 2000 Dec |
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The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. | 2000 Jan |
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Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study. | 2000 Jun |
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Experimental model of hepatic venoocclusive disease (VOD) caused by dactinomycin--preliminary report about hepatoprotective effect of amifostine. | 2000 May-Jun |
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[Current approaches in prevention and therapy of chemo- and radiotherapy-induced oral mucositis]. | 2001 |
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WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment. | 2001 |
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Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia. | 2001 |
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Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany. | 2001 |
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T-cell apoptosis induced by granulocyte colony-stimulating factor is associated with retinoblastoma protein phosphorylation and reduced expression of cyclin-dependent kinase inhibitors. | 2001 Apr |
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Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma. | 2001 Aug 15 |
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A randomized phase II study of amifostine used as stem cell protectant in non-hodgkin lymphoma patients receiving cisplatin-based salvage chemotherapy prior to stem cell transplant. | 2001 Dec |
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Effect of amifostine on toxicities associated with salvage combination chemotherapy. | 2001 Feb |
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Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome. | 2001 Feb |
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Bone marrow stem cell protection from chemotherapy by low--molecular-weight compounds. | 2001 Feb |
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Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. | 2001 Feb 15 |
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A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. | 2001 Feb 2 |
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Anticancer drug-induced kidney disorders. | 2001 Jan |
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A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer. | 2001 Jan 5 |
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Phase I-II study of escalating doses of amifostine combined with high-dose cyclophosphamide. | 2001 Jun |
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Effect of amifostine on lipid peroxidation caused by cisplatin in rat kidney. | 2001 Jun |
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Selective radioprotection of hepatocytes by systemic and portal vein infusions of amifostine in a rat liver tumor model. | 2001 Jun 1 |
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Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay. | 2001 Jun 14 |
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Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. | 2001 Mar |
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Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. | 2001 Mar |
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Clarification on the potential of subcutaneous ethyol as a radioprotective agent. | 2001 Mar 1 |
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[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study]. | 2001 May |
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A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188). | 2001 Nov 15 |
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Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice. | 2002 |
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Radioprotection of head and neck tissue by amifostine. | 2002 |
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Relationships between cytoprotection and mutation prevention by WR-1065. | 2002 Feb |
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New dosing regimens for amifostine: a pilot study to compare the relative bioavailability of oral and subcutaneous administration with intravenous infusion. | 2002 Feb |
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Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells. | 2002 Feb 15 |
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Rationale for a phase I/II radiation dose-escalation study with concurrent amifostine (Ethyol) and infusional 5-FU chemotherapy for preoperative treatment of unresectable or locally recurrent rectal carcinoma. | 2002 Jan |
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Intrarectal application of amifostine for the prevention of radiation-induced rectal injury. | 2002 Jan |
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Phase II evaluation of amifostine as an esophageal mucosal protectant in the treatment of limited-stage small cell lung cancer with chemotherapy and twice-daily radiation. | 2002 Jan |
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Phase II: trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy. | 2002 Jan |
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Influence of amifostine on the toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients: a pilot study. | 2002 Jan |
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Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients. | 2002 Jan 1 |
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Inhibition of spontaneous metastases formation by amifostine. | 2002 Jan 10 |
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Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes. | 2002 Mar |
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Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. | 2002 Mar 1 |
Patents
Sample Use Guides
For Reduction of Cumulative Renal Toxicity with Chemotherapy:
The recommended starting dose is 910 mg/m2 administered once daily as a 15-minute infusion.
For Reduction of Moderate to Severe Xerostomia from Radiation of the Head and Neck:
The recommended dose is 200 mg/m2 administered once daily as a 3-minute infusion starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).
infusion, starting 30 minutes prior to chemotherapy.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
Human pulmonary EC were grown on golden microelectrodes. Cells were pretreated with WR-1065 (unprotected form of amifostine, used for cell culture treatments) (0.4 mM, 1 mM or 4 mM, 30 min) followed by stimulation with 250 mM H2O2 (Panel A). EC were pretreated with 4 mM
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:25:30 GMT 2025
by
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Record UNII |
M487QF2F4V
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Record Status |
Validated (UNII)
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Record Version |
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FDA ORPHAN DRUG |
128399
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FDA ORPHAN DRUG |
116298
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WHO-VATC |
QV03AF05
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FDA ORPHAN DRUG |
24187
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FDA ORPHAN DRUG |
42989
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FDA ORPHAN DRUG |
111698
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NDF-RT |
N0000180854
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FDA ORPHAN DRUG |
42789
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NCI_THESAURUS |
C2080
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FDA ORPHAN DRUG |
42889
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LIVERTOX |
36
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WHO-ATC |
V03AF05
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DD-7
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DB01143
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4126
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M487QF2F4V
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AMIFOSTINE
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1019406
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m1669
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100000091456
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C488
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DTXSID40150210
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SUB27016
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2636
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M487QF2F4V
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CHEMBL1006
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112901-68-5
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148139
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ANHYDROUS->SOLVATE | |||
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PARENT -> SALT/SOLVATE |
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ASSAY (HPLC)
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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