Mechanisms of reaction of L‐methionine with carboplatin and oxaliplatin in different media: a comparison with cisplatin

The activity of platinum compounds is dependent on nucleophile substitution reactions. In this paper, we study the reactivity of L‐met with carboplatin, oxaliplatin and cisplatin by following with HPLC‐UV the concentration of L‐met and by characterizing the resulting adducts with LC‐MS. In the absence of NaCl, in water, the initial rate at which L‐met concentration decreases with cisplatin, oxaliplatin and carboplatin is 0.25±0.007, 0.057±0.01 and 0.17±0.02 mM h−1, respectively. In phosphate buffer this rate is 0.056±0.009 for cisplatin, 0.019±0.001 and 0.13±0.02 for carboplatin and oxaliplatin, respectively. Reactions of L‐met with cisplatin occurred via its conversion into monoaqua species in water and into phosphato‐derivatives (AP) in phosphate buffer but finally the same methionine–platinum adducts M2 [(NH3)2(met)]Pt, M4 and M5 [(met)2]Pt were characterized. Reaction of carboplatin with l‐met occurred via the formation of M0 [(NH3)2(met)(CBDCA)]Pt whose structure is consistent with the direct interaction of L‐met with carboplatin. However, the same final products as those found with cisplatin were characterized. The reaction of oxaliplatin with L‐met proceeded through a mechanism similar to that of carboplatin to give M7 [(met)(DACH)]Pt. In the presence of NaCl, cisplatin directly reacted with L‐met to yield at least five methionine–platinum adducts. The reaction of carboplatin gave the same adducts suggesting its transformation into cisplatin. The reaction of oxaliplatin with L‐met occurred via the formation of aquated species A [(OH)(Cl)(DACH)]Pt which readily underwent reaction with L‐met to form M6 [(met)(Cl)(DACH)]Pt and M7. This study shows that the reactivity of cisplatin, carboplatin and oxaliplatin is dependent on the media in which they occur. The discrepancy between their reactions with L‐met could partly explain their therapeutic differences. Copyright © 1999 John Wiley & Sons, Ltd.

[1]  A. Cailleux,et al.  Kinetic studies of the reactivity between cisplatin and its monoaquo species with L-methionine , 1998 .

[2]  S. Duffull,et al.  Clinical Pharmacokinetics and Dose Optimisation of Carboplatin , 1997, Clinical pharmacokinetics.

[3]  R. Carballar,et al.  Stability study of carboplatin in aqueous solution and under illumination by high performance liquid chromatography. , 1997, Biomedical chromotography.

[4]  S. Ghosh,et al.  Kinetic analysis of the cis-diamminedichloroplatinum(II)--cysteine reaction: implications to the extent of platinum--DNA binding. , 1997, Journal of inorganic biochemistry.

[5]  R. Rietbroek,et al.  In vitro formation of DNA adducts by cisplatin, lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells. , 1996, Carcinogenesis.

[6]  H. Ogata,et al.  Decomposition Kinetics of Cisplatin in Human Biological Fluids , 1996, The Journal of pharmacy and pharmacology.

[7]  Peter J. Sadler,et al.  Ring-Opened Adducts of the Anticancer Drug Carboplatin with Sulfur Amino Acids. , 1996, Inorganic chemistry.

[8]  B. Casetta,et al.  Characterization of cisplatin-glutathione adducts by liquid chromatography-mass spectrometry. Evidence for their formation in vitro but not in vivo after concomitant administration of cisplatin and glutathione to rats anc cancer patients. , 1995, Journal of chromatography. B, Biomedical applications.

[9]  P. Sadler,et al.  [Pt(CBDCA-O)(NH3)2(L-Methionine-S)]: Ring-Opened Adduct of the Anticancer Drug Carboplatin ("Paraplatin"). Detection of a Similar Complex in Urine by NMR Spectroscopy , 1994 .

[10]  L. Pendyala,et al.  In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. , 1993, Cancer research.

[11]  P. Sadler,et al.  Ring‐Opening Reactions of the Anticancer Drug Carboplatin: NMR Characterization of cis‐(Pt(NH3)2(CBDCA‐O)(5′‐GMP‐N7)) in Solution. , 1993 .

[12]  J. Dorsey,et al.  Determination of cisplatin and some possible metabolites by ion-pairing chromatography with inductively coupled plasma mass spectrometric detection. , 1993, Journal of chromatography.

[13]  P. Sadler,et al.  Cis-trans isomerization of [bis(L-methioninato)platinum]: metabolite of the anticancer drug cisplatin , 1993 .

[14]  P. Sadler,et al.  Studies of platinum(II) methionine complexes : metabolites of cisplatin , 1992 .

[15]  M. Esposito,et al.  Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin. , 1988, Anticancer Research.

[16]  B. Corden.  Reaction of platinum(II) antitumor agents with sulfhydral compounds and the implications for nephrotoxicity , 1987 .

[17]  P. Dedon,et al.  Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles. , 1987, Biochemical pharmacology.

[18]  H. Pinedo,et al.  Interaction of cisplatin and carboplatin with sodium thiosulfate: reaction rates and protein binding. , 1986, Clinical chemistry.

[19]  D. Lydall,et al.  Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) differ only in the kinetics of their interaction with DNA. , 1986, Cancer research.

[20]  C. Riley,et al.  Monitoring the reactions of cisplatin with nucleotides and methionine by reversed-phase high-performance liquid chromatography using cationic and anionic pairing ions. , 1983, Analytical biochemistry.

[21]  F. Hochberg,et al.  Trace analysis for cis-platinum anti-cancer drugs via LCEC. , 1983, Journal of chromatographic science.

[22]  P. Daley-Yates,et al.  The inhibition of renal ATPase by cisplatin and some biotransformation products. , 1982, Chemico-biological interactions.

[23]  K. Kohn,et al.  Mechanism of action of cis-dichlorodiammineplatinum(II). , 1979, Cancer treatment reports.

[24]  B. Rosenberg.  Anticancer activity of cis-dichlorodiammineplatinum(II) and some relevant chemistry. , 1979, Cancer treatment reports.

[25]  BARNETT ROSENBERG,et al.  Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode , 1965, Nature.

[26]  T. Hambley,et al.  Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin. , 1997, British Journal of Cancer.

[27]  C. Louvet,et al.  Place et intérêt de l'oxaliplatine dans les cancers colorectaux métastasés , 1997 .

[28]  A. Cailleux,et al.  Interactions between cisplatin derivatives and mobile phase during chromatographic separation , 1997 .

[29]  J. Cradock,et al.  Stability of cisplatin, iproplatin, carboplatin, and tetraplatin in commonly used intravenous solutions. , 1987, American journal of hospital pharmacy.

[30]  A. Repta,et al.  Exacerbation of cisplatin-induced nephrotoxicity by methionine. , 1984, Chemico-biological interactions.

[31]  A. Balch,et al.  195Pt and 31P nuclear magnetic resonance studies of the binding of the cis-Pt(NH3)2+2 moiety to phosphate in aqueous solution , 1982 .

[32]  A. Repta,et al.  REACTIONS OF CISPLATIN WITH HUMAN PLASMA AND PLASMA FRACTIONS , 1980 .