Melphalan hydrochloride

Spectra of Melphalan and Melphalan Hydrochloride in KBr dispersions are shown in Figures 2 and 3. 

Figure 3. Infrared Spectrum of Melphalan Hydrochloride (undried). KBr pellet. Instrument—Perkin Elmer 727.

Proton magnetic resonance spectra of melphalan in dimethylsulfoxide (DMSO)-dg and D2O—DC1 solutions and of melphalan hydrochloride in DMSO-dg are shown in Figure 4. The spectra were run on a Varian FT-80A spectrometer at 80 MHz. The assignments of the chemical shifts are tabulated in Table I. 

A) Melphalan In DMSO-d6. (B) Melphalan Hydrochloride In DMSO-d6. (C) Melphalan In C O-DCI... 

Melphalan Injection is defined as a sterile solution of melphalan hydrochloride. It is available commercially as a kit comprising melphalan in a sealed... 

Melphalan Hydrochloride for Injection (Alkeran ) exemplifies the application of cosolvency. The drug is supplied as a lyophilized powder with a sterile diluent for reconstitution that is comprised of sodium citrate (0.2 g), propylene glycol (6.0 mL), ethanol (96% grade, 0.52 mL), and Water for Injection, diluted to a total volume of 10 mL. ALKERAN for Injection is administered intravenously. 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

C HiiNOj 63-91-2) see Melphalan Quinapril hydrochloride Saquinavir L-phenylalanine fert-hutyl ester hydrochloride (CijHtoCINOj 15100-75-1) see Alacepril D-phenylalanine methyl ester (CioHijNOj 21685-51-8) see Nateglinide L-phenylalanine methyl ester hydrochloride (C10H14CINO2 7524-50-7) see Angiolensinatnide... 

Cj H403 85-44-9) sec Anisindione Chlortalidone Cilazapril Deptropine Fluorescein Hydralazine Indobufen Indoprofen Melphalan Phenolphthalein Phthalylsulfathiazole Pizotifen Pramipexole hydrochloride Saquinavir Sulfaloxic acid Thalidomide Tilisolol hydrochloride phthalide... 

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

ClCH2CH2)2NC6H4CH2CH(NH2)COOH. Melphalan is both the USAN name for the acid and the generic name for the hydrochloride. 

Examples of substances that are prone to hydrolysis are acetylsalicylic acid, ampicillin, barbiturates, chloramphenicol, chlordiazepoxide, cocaine, corticosteroid phosphate or succinate esters, proteins, folinic acid, indomethacin, local anaesthetics, paracetamol (acetaminophen), pilocarpine, tropa alkaloids (atropine, scopolamine), xylomethazoline and the antimicrobial preservatives methyl and propyl parahydroxybenzoate. In the field of oncology, melphalan and bendamustine hydrochloride are highly susceptable to hydrolysis with a shelf life of 1.5 h for melphalan and 3.5 h for bendamustine at room temperature. 

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