Extent of cisplatin formation in carboplatin admixtures.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
J B Bogardus
Publications and source records attributed to J B Bogardus.
Degradation kinetics and mechanism of N6-[(dimethylamino)methylene]mitomycin C in aqueous solutions.
The degradation of N6-[(dimethylamino)methylene]mitomycin C, a semisynthetic analogue of mitomycin C, was studied in aqueous solution. The compound degraded rapidly and followed pseudo-first-order kinetics in both acidic (pH less than 5) and basic pH greater than or equal to 9) media. In the near-neutral pH region, however, biphasic kinetics were observed. At the pH of maximum stability (6.5), 10% activity was lost after approximately 6 h at 22 degrees C. Citrate and phosphate species were catalytic at pH 6.5. Spectrophotometric and HPLC methods were used to elucidate the degradation mechanism at pH 7-9. Under these conditions, equilibrium addition of one water molecule into the amidine side chain occurred, followed by parallel formation of mitomycin C and N6-(formyl)mitomycin C. The latter compound subsequently hydrolyzed to mitomycin C.
Buffers↗
S-acylation of cysteine by O-acetylsalicylic anhydride: a possible mechanism for aspirin hypersensitivity?
In order to elucidate the possible reaction pathways for the acylation of protein by O-acetylsalicylic anhydride, the mechanism of the reaction between L-cysteine and O-acetylsalicylic anhydride was studied. O-Acetylsalicylic anhydride reacts with L-cysteine via a consecutive kinetic pathway. The thiol anion first reacts with the anhydride to form an intermediate thiol ester which then undergoes an intramolecular rearrangement to form the stable N-(O-acetylsalicyloyl)-2-amino-3-thiopropionic acid, 5. The importance of the free amino group in the intramolecular reaction was established by the observed stability of the S-(O-acetylsalicyloyl) derivative of N-acetylcysteine under similar reaction conditions. The formation of the thiol ester was pH dependent, suggesting that the thiol anion was the attacking species. The acyl transfer to the adjacent amino group was catalyzed by both phosphate and acetate buffers. The results suggest that the reaction of O-acetylsalicylic anhydride with the thiol-containing amino acids of a protein molecule may proceed via formation of an initial thio ester, followed by an S to N intramolecular acyl transfer to form an immunogenic amide.
Acylation↗
Solubility of doxycycline in aqueous solution.
The solubility of doxycyline monohydrate and doxycycline hydrochloride dihydrate was investigated in aqueous solution. The hydrochloride dihydrate salt was isolated and identified from solutions initially containing doxycycline hyclate in water. The pKa' = 3.09 (mu = 0.1 and 25 degrees) for protonation of doxycycline was determined spectrophotometrically. The pH-solubility profiles were determined for doxycycline monohydrate in water and in 1.0 M NaNO3-HNO3 and NaCl-HCl. The pH-solubility profile at 25 degrees for doxycycline in aqueous hydrochloric acid without added salt reached a sharp maximum fo 50 mg/ml at pH 2.16. Added chloride ion strongly suppressed the solubility of the hydrochloride dihydrate salt. The apparent solubility product was not constant but decreased as the concentration of added salt increased. A theoretical model was developed involving dimerization of doxycycline and applied to the experimental data. The dimerization constant, Kd = 24 M-1, and true solubility product, K0sp = 1.8 X 10(-3) M2, were calculated. The effect of concentration on NMR and visible spectra indicated that dimerization resulted from intermolecular hydrogen bonding of the phenolic beta-diketone portion of the molecule.
Doxycycline↗
Dissolution rates of doxycycline free base and hydrochloride salts.
The dissolution rates of doxycycline monohydrate, hyclate, and hydrochloride dihydrate crystal forms were investigated using the static pellet method. Solubility product equilibria with chloride ion strongly suppressed the dissolution rate of the hydrochloride dihydrate salt. This form dissolved about fourfold slower in 0.1 N HCl than in water, which was consistent with its solubility in these media. Specificity for chloride was demonstrated by the rapid dissolution rate for the hydrochloride dihydrate in 0.1 N methanesulfonic acid. The dissolution rates of the hyclate, a solvated hydrochloride salt, and the free base were not sensitive to chloride ion. The results show that common ion equilibria with chloride can strongly reduce the dissolution rate of a thermodynamically stable hydrochloride salt form, while the free base or a metastable hydrochloride salt are not similarly affected.
Buffers↗