CARBOPLATIN

PRODUCT IDENTIFICATION
CAS NO. 41575-94-4; 70903-55-8

CARBOPLATIN
EINECS NO. 255-446-0
FORMULA [C4H6(CO2)2]Pt(NH3)2
MOL WT. 371.25

H.S. CODE

 2843.90.0000

TOXICITY

 Oral Rat LD50: 343mg/kg
SYNONYMS 1,1-Cyclobutanedicarboxylatodiammine Platinum (II);
1,1-Cyclobutanedicarboxylate diamine platinum(II); Paraplatin; cis-(1,1-Cyclobutane dicarboxylato) diamineplatinum(II); cis-Diamine (1,1-cyclobutaned icarboxylato) platinum(II); (SP-4-2)- diamine (1,1-cyclobutanedicarboxylato (2-)-O,O')-platinum (II); Carboplatine; Carboplatino; Diammine(1,1-cyclobutanedicarboxylato)platinum (II); Diammine-1,1-cyclobutane dicarboxylate platinum II;
SMILES C12(C(=O)O[Pt](OC1=O)([NH3])[NH3])CCC2

CLASSIFICATION

 Antineoplastic Agent; Cross-Linking Reagent; Indicator; Platinum-based drug;

PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE white crystalline powder
MELTING POINT  
BOILING POINT  
SPECIFIC GRAVITY  
SOLUBILITY IN WATER Soluble
pH  
VAPOR DENSITY

 

AUTOIGNITION

 
log Pow -0.46 (Octanol-water)
OH RATE 1.19E-12 (cm3/molecule-sec at 25 C Atmospheric)

NFPA RATINGS

  

REFRACTIVE INDEX

 
FLASH POINT  
STABILITY

Stable under ordinary conditions

GENERAL DESCRIPTION & APPLICATIONS
Carboplatin, a platinum coordination compound which contains a platinum atom surrounded with two ammonia groups and two other ligands in a ring structure. Cisplatin is an analogue which has two chloride atoms instead of ring structure. Oxaliplatin contains a platinum atom complexed with 1,2-diaminocyclohexane and with an oxalate ligand as a leaving group. It is known that diaminocyclohexane group contributes greater cytotoxicity than cisplatin and carboplatin. Oxaliplatin is not generally cross-resistant to cisplatin or carboplatin. They are capable of forming platinum complexes producing inter- and intrastrand DNA crosslinks with neighboring guanine residues, resulting in DNA-mismatch repair (MMR) activity in the cancer cells. Carboplatin has less nephrotoxicity, neurotoxicity, ototoxicity and emetogenesis and more stability than cisplatin. They, platinum-based antineoplastics, have a broad spectrum of antitumor activity in the treatments of carcinomas of ovarian, testicular, bladder, small and non–small cell lung, head and neck carcinoma, and seminoma. They are synergistic with fluorouracil. They are radiation sensitive. The chemical designation of cisplatin is (SP-4-2)-diaminedichloroplatinum (II). It is a yellow crystalline powder; soluble in water and saline; administered intravenously. The chemical designation of carboplatin is (SP-4-2)-diammine [1,1-cyclobutanedicarboxylato (2-)-0, 0']- platinum (II). It is a white crystalline powder; soluble in water; insoluble in ethanol, acetone, and dimethylacetamide; administered intravenously. The chemical designation of oxaliplatin is SP-4-2-(1R-trans))- (1,2-cyclohexanediamine-N,N')- (ethanedioato(2-)-O,O') platinum (II). It is a white crystalline powder; soluble in water; very slightly soluble in methanol; insoluble in ethanol, hexane, benzene and acetone.

Wikipedia Linking: http://en.wikipedia.org/

Google Scholar Search: http://scholar.google.co.kr/

http://jco.ascopubs.org/
Carboplatin (CBDCA, Bristol-Meyers, New York) is a second generation platinum analog. Preclinical and phase I clinical studies have indicated a different spectrum of toxicity compared with the parent compound. In order to study the activity of carboplatin against cancer of the head and neck, 31 patients with recurrent or metastatic disease (30 squamous-cell and one adenoid cystic carcinoma) were treated with doses of 60 to 80 mg/m2 administered daily by intravenous (IV) bolus injections for five days, repeated at every 4- to 5-week intervals. In most cases, treatment was administered on an outpatient basis. Eight patients (26%; 95% confidence interval, 12% to 45%) had complete (CR) or partial responses (PR) with a median duration of 4.5 months. Moderate bone marrow suppression was the main toxicity. Mild nausea and vomiting was unusual and no neuro- or nephrotoxicity were seen. These preliminary data suggest that carboplatin has activity against advanced squamous-cell carcinoma of the head and neck comparable with the results reported with cisplatin alone in similar patient populations. The potential advantages over the parent compound relate to the absence of nephrotoxic effects and mild gastrointestinal toxicity which allows for outpatient treatment. Because carboplatin toxicity is directly dependent on its mechanism of renal excretion, particular attention should be given for its use in patients with impaired renal function or when combined with nephrotoxic agents. Similarly, because the dose limiting toxicity with this agent is primarily hematologic, its use in combination with other myelotoxic agents should be carefully undertaken. Further studies are indicated in order to define the spectrum of activity of the new generation platinum analogs in various tumors in humans...

http://www.getwellpharma.org/
Mechanism of Action

  • Carboplatin is a cisplatin analog with similar antineoplastic activity, but with a different adverse effect profile than cisplatin. Carboplatin has a carboxycyclobutane moiety replacing the chloride atoms on cisplatin. Both agents are cell cycle-nonspecific and share a similar mechanism of action.
  • The major antineoplastic mechanism of action for cisplatin and carboplatin is the production of crosslinks within and between strands of deoxyribonucleic acid (DNA). Normal DNA synthesis is inhibited by this disruption of cellular DNA conformation. The dicarboxylate group on carboplatin is much more stable than the chloride groups on cisplatin, and this may possibly affect the antitumor properties of the compound. In vitro and in vivo studies indicate that the differences in cytotoxicity between cisplatin and carboplatin may be related to the kinetics of their interaction with DNA.
  • Cisplatin breaks down to unstable hydrolysis products which are rapidly bound to plasma proteins and extensively filtered, with some active secretion, by the kidney, this high renal concentration is thought to be the major cause of nephrotoxicity. Carboplatin may be less nephrotoxic than cisplatin because carboplatin is more soluble and chemically stable and binds more slowly to plasma proteins. In vitro and in vivo studies indicate that the differences in cytotoxicity between cisplatin and carboplatin may be related to the kinetics of their interaction with DNA.
SALES SPECIFICATION

APPEARANCE

 white crystalline powder

IDENTIFICATION

Complies Test A,B

ASSAY

98.0 - 102.0% (HPLC)

PLATINUM CONTENT

52.0 - 53.0%

RELATED SUBSTANCE

0.5% max (1,1-Cyclobutane dicarboxylic acid)

WATER

0.5% max

INSOLUBLES IN WATER

0.5% max

pH

5.0 - 7.0 (10mg/ml in water)

CLARITY

Complies

SILVER

 10ppm max
BARIUM 10ppm max
TRANSPORTATION
PACKING
 
HAZARD CLASS 6.1 (Packing Group:III)
UN NO. 2811
OTHER INFORMATION
Hazard Symbols: T , Risk Phrases: 46-61-20/21/22-42/43, Safety Phrases: 53-22-26-36/37/39-45

GENERAL DESCRIPTION OF ALKYLATING AGENTS AS ANTITUMOR
Alkylating agents are used in cancer chemotherapy by the substitutiopn of alkyl groups for the hydrogen atoms in biological organic compounds present in cells to inhibit tumor growth with mutagenic activity. They cross-links DNA, makes the strands unable to seperate, and induces mutations. They are cell cycle non-specific drugs. Their effects primarily occurs in proliferating tissues which don't have time to mitose DNA repair systems. Classes of alkylating agents for antineoplastic include:
  • Nitrogen mustard
    • Chlorambucil (CAS RN: 305-03-3)
    • Mechlorethamine (CAS RN: 51-75-2)
    • Melphalan (CAS RN: 148-82-3)
    • Uracil Mustard (CAS RN: 66-75-1)
    • Cyclophosphamide (CAS RN: 50-18-0)
    • Iphosphamide (CAS RN: 3778-73-2)
  • Nitrosoureas
    • Triethylenemelamine (CAS RN: 51-18-3)
    • Hexamethylmelamine (CAS RN: 645-05-6)
    • Bis-chloroethylnitrosourea (CAS RN: 154-93-8)
    • Chloroethylcyclohexylnitrosourea (CAS RN: 13010-47-4)
    • Streptozotocin (CAS RN: 18883-66-4)
  • Platinum compounds
    • Carboplatin (CAS RN: 41575-94-4)
    • Oxaliplatin (CAS RN: 61825-94-3)
    • Cisplatin (CAS RN: 15663-27-)
    • Tetraplatin (CAS RN: 62816-98-2)
    • (Carboxyphthalato)platinum (CAS RN: 65296-81-3)
  • Alkyl sulfonates
    • Busulfan (CAS RN: 55-98-1)
  • Aziridines
    • Thiotepa (CAS RN: 52-24-4)