Irinotecan hydrochloride trihydrate Chemical Properties

Melting point:

250-256°C (dec.)

Boiling point:

257°C(lit.)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 50 mg/ml), in Water (up to 4 mg/ml) or in Ethanol (up to 4 mg/ml).

form 

White solid.

color 

Yellow

Water Solubility 

Soluble in DMSO at 100mg/ml. Soluble in water at 25mg/ml with warming

Merck 

14,5091

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO, ethanol or distilled water may be stored at -20° for up to 3 months.

InChIKey

KLEAIHJJLUAXIQ-VRWBIZLENA-N

SMILES

N1(C2CCN(C(OC3C=CC4C(C=3)=C(CC)C3CN5C(C=3N=4)=CC3[C@](CC)(O)C(=O)OCC=3C5=O)=O)CC2)CCCCC1.[H]Cl.[H]O[H].[H]O[H].[H]O[H] |&1:24,r|

CAS DataBase Reference

136572-09-3(CAS DataBase Reference)

Safety Information

Risk Statements 

22

Safety Statements 

20/21-22

RTECS 

DW1060750

HS Code 

29349990

Toxicity

dog,LD50,intravenous,40mg/kg (40mg/kg),Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 26, Pg. 953, 1995.

Irinotecan hydrochloride trihydrate Usage And Synthesis

Description

Irinotecan (136572-09-3) is a semi-synthetic derivative of camptothecin (Cat.# 10-1041) that is an FDA approved anticancer drug. It is a prodrug that is converted by tissue esterases to 7-ethyl-10-hydroxycamptothecin (SN-38, Cat.# 10-2425), a potent inhibitor of DNA topoisomerase I.1,2 Although irinotecan is also a topoisomerase inhibitor, SN-38 is approximately 1000 times as potent in purified enzyme studies. In vitro cytotoxicity assays show much greater variability in potency between the two (2-2000 fold).3

Chemical Properties

White powder

Uses

Irinotecan Hydrochloride Trihydrate is a DNA topoisomerase inhibitor.

Definition

ChEBI: A hydrate that is the trihydrate form of irinotecan hydrochloride. Onivyde is used in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine based therapy. It is converted via hydrolysis of the carbamate linkage to its active metabolite, SN-38, which is ~1000 times more active.

brand name

Camptosar (Pharmacia &Upjohn) .

Hazard

Moderately toxic by ingestion.

Synthesis

(S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4';6,7]indolo[1,2-b]quinolin-9-yl[1,4'-bipiperidin]-1'-carboxylic acids were synthesized using (S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3. 4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl [1,4'-bipiperidin]-1'-carboxylate trihydrate in the following general procedure: irinotecan hydrochloride (4.8 g), water (30 mL), ethanol (10 mL), and 5% hydrochloric acid solution (0.3 mL) were added to the reaction flask. The reaction mixture was heated to 75-80°C with continuous stirring until complete dissolution. Subsequently, the solution was cooled to 65°C and crystallization was induced by the addition of crystal seeds. The rate of cooling was controlled so that the solution was slowly cooled to 50 °C over 10 hours and then continued to 20 °C over the next 10 hours. Upon completion of crystallization, the solid product was collected by filtration and washed with pure water (16 mL). The resulting product was dried at room temperature and under atmospheric pressure to give 4.6 g of irinotecan hydrochloride trihydrate in 87% yield. The purity of the product was 99.9% by high performance liquid chromatography (HPLC). The structure of the product was confirmed by X-ray diffraction and infrared spectroscopy (IR) analysis to be consistent with form b as described in WO 03/074527. Microscopic observation showed that the average length of the crystals ranged from 50 μm to 200 μm.

References

[1] T KUNIMOTO. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.[J]. Cancer research, 1987, 47 22: 5944-5947.
[2] R. MATHIJSSEN. Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan.[J]. Current cancer drug targets, 2002, 220 1: 103-123. DOI:10.2174/1568009023333890
[3] Pfizer drug scores a KO[J]. Inpharma Weekly, 1992, 16 1: 22. DOI:10.2165/00128413-199208570-00044

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