Bendamustine Hydrochloride

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Cat Number

API0232136

CAS Number

3543-75-7

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CAS Number

3543-75-7

EINECS

631-540-0

Storage

Store at 2-8°C

Synonyms

Bendamustine HCl; Treanda; Ribomustin; Bendamustin hydrochloride; Bendeka; Ribomustine; Levact; NSC-138783; SYBL-0501

Molecular Formula

C16H22Cl3N3O2

Molecular Weight

394.7

Smiles

CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCC(=O)O.Cl

Appearance

Pale brown crystalline powder

Melting Point

149-151°C

General Description

Bendamustine hydrochloride is a unique alkylating agent containing a benzimidazole ring and a nitrogen mustard moiety. Its structure combines the properties of purine analogues and classical alkylators, allowing it to form covalent crosslinks with DNA. The hydrochloride salt improves aqueous solubility and stability. This dual functionality distinguishes bendamustine from other chemotherapeutic agents.

Mechanism of Action

Bendamustine induces cell death primarily through DNA crosslinking via alkylation at the N7 position of guanine. The resulting interstrand and intrastrand crosslinks cause replication fork collapse, cell cycle arrest, and apoptosis. Unlike many alkylators, bendamustine has only partial cross-resistance with other agents due to its distinct mechanism of activation and reduced repair by mismatch repair pathways.

Application

Bendamustine is indicated for the treatment of chronic lymphocytic leukemia (CLL) and indolent B‑cell non‑Hodgkin lymphoma that has progressed during rituximab‑containing therapy. It is also effective in multiple myeloma and mantle cell lymphoma. The drug demonstrates activity in patients refractory to other alkylating agents, and it exhibits a manageable toxicity profile.

This overview summarizes bendamustine pharmacokinetics in hematologic malignancies. Bendamustine peaks at end of 1‑hour infusion, with triphasic elimination; the intermediate half‑life (~40 min) is the effective one. It is rapidly hydrolyzed to inactive metabolites; CYP1A2 oxidation produces active metabolites but contributes minimally to cytotoxicity, implying low risk of drug‑drug interactions with CYP1A2 inhibitors. Systemic exposure is comparable between adults and children; age, race, and sex have no significant effect. No clear exposure‑efficacy relationship exists, but higher exposure may increase nausea or infection risk. Dosing based on body surface area is supported.

Fig. 1 Bendamustine and its main metabolites. (Darwish M, et al., 2015)

References

Darwish M, et al. Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015;75(6):1143-1154.

This review examines the immunomodulatory properties of bendamustine in hematopoietic cell transplantation (HCT). In murine models, pre‑ and post‑transplant bendamustine reduced graft‑versus‑host disease (GvHD) and enhanced graft‑versus‑leukemia (GvL) effects by altering T‑cells, myeloid‑derived suppressor cells, and dendritic cells. In vitro, bendamustine enhances MDSC suppressive function, skews DCs toward cDC1s, increases IL‑10 production from B‑cells, and suppresses STAT3 activation. These properties are being explored in ongoing clinical trials to improve allogeneic HCT outcomes.

Fig. 2 Summary of the immunomodulatory effects of bendamustine observed in murine models and in vitro systems. (Stokes J, et al., 2021)

References

Stokes J, et al. Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation. Cancers (Basel). 2021;13(7):1702.

Does Bendamustine Hydrochloride require strict cold chain storage as a nitrogen mustard?

Yes, it must be stored at 2-8°C. At room temperature, rapid hydrolysis and degradation of the alkylating moieties occur, leading to potency loss.

Is Bendamustine Hydrochloride sensitive to light and moisture?

Yes, it is both photosensitive and hygroscopic. Store in original, tightly sealed, light-resistant containers with desiccant under refrigeration.

What is the stability of Bendamustine Hydrochloride after reconstitution for intravenous infusion?

Reconstituted solutions degrade very rapidly (within 2-3 hours at room temperature). Use immediately after preparation.

How is the impurity HP1 (a major hydrolysis product) monitored?

This primary degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH limits.