O.A.G.J. van der Houwen

Aspects of the degradation kinetics of doxorubicin in aqueous solution

Abstract The chemical stability of doxorubicin in aqueous solution has been investigated utilizing a stability-indicating HPLC assay with UV-VIS and fluorescence detection. The degradation kinetics were studied as function of pH (1–11), buffer composition (acetate, phosphate, carbonate), ionic strength (μ= 0.1–0.4), temperature (30–70°C) and drug concentration (1–20 μg/ml). A pH-rate profile, obtained from first-order kinetic plots, corrected for buffer and ionic strength influences, was constructed. The pH profile shows maximum stability for doxorubicin at about pH 4. A theoretical description of the pH-rate profile is presented. In addition, some attention has been given to the degradation mechanism of doxorubicin in alkaline solution. The proposed mechanism is partly based on a comparison of the chemical stability of doxorubicin with daunorubicin and five related anthracycline agents.

Ion-exchange phenomena and concomitant pH shifts on the equilibration of reversed-phase packings with ion-pairing reagents

Abstract Breakthrough patterns of eluents containing tetrabutylammonium or cetyltrimethylammonium ions (two frequently used ion-pairing agents in high-performance liquid chromatography) have been studied, using reversed-phase columns with octadecyl chains permanently bonded to 10-μm silica particles. The occurrence of pH shifts either before or after the breakthrough of the ion-pairing agents has been demonstrated. An explanation for the breakthrough patterns is offered and evidence for two different binding mechanisms of these agents is presented.

Degradation kinetics of etoposide in aqueous solution

Abstract The chemical stability of the anticancer drug etoposide in aqueous solution has been investigated utilizing a stability-indicating reversed-phase high-performance liquid Chromatographie assay with ultraviolet detection. The degradation processes can adequately be described by pseudo-first order kinetics. The degradation kinetics have been studied as function of pH, buffer composition, ionic strength and temperature. A pH-rate profile, using rate constants extrapolated to zero buffer concentration, was constructed demonstrating that etoposide is most stable in the pH region 4–5. A comparison between the chemical stabilities of etoposide and podophyllotoxin in the pH region 9–11 has been made. The degradation mechanism of etoposide in aqueous solution is discussed.

A general approach to the interpretation of pH degradation profiles

Abstract A general equation for pH-dependent degradation profiles of polybasic weak electrolytes is presented. The potential information which can be deducted from such profiles is discussed. The method is graphically illustrated with a hypothetical example.

Evaluation of the Use of Lithium Nitrate as a Test Substance for the Determination of the Hold-Up Time of a Reversed-Phase Packing

Abstract The use of lithium nitrate as a test substance for the determination of the hold-up time on μ Bondapak C18 columns has been evaluated by comparison with the hold-up time calculated with the homologous series of n-alcohols. The influence of charge exclusion effects on the retention time of lithium nitrate is investigated. The addition of phosphoric acid to the eluent appears to be an effective method to reduce charge exclusion effects. The existence of deviations from linearity are demonstrated for the homologous series of n-alcohols in eluents with a low methanol content.

Systematic interpretation of pH-degradation profiles. A critical review

In this study we discuss the application of the general models for pH degradation profiles for specific acid, solvent and base catalysis, both in the absence and presence of ligands, and for the general acid and base catalysis, that we have published recently, we also present a systematic step by step procedure for the interpretation of pH profiles, which we apply to a number of recent publications. To facilitate the comparison of the mathematical treatment of the data the model equations reported in these studies have been transformed analogous to our equations. Many of these studies raise minor to serious objections. These objectives vary from unjustified conclusions regarding the content of specific reactions to the degradation, mathematical errors in the model equations, unjustified neglect of pKa values close to or within the pH range investigated, unjustified linearization of non linear relationships to the application of model equations with non integer exponents without any theoretical foundation. Application of our model equations explains discrepancies in some of the original publications and offers acceptable alternatives to some rather stretched hypotheses.

Degradation kinetics of vinblastine sulphate in aqueous solutions

Abstract The degradation kinetics of vinblastine sulphate (VBL) have been studied over the H 0 /pH range −4 up to 14 at 80°C. A stability indicating HPLC-system with UV-detection was used to separate the parent compound and the degradation products. The influences on the degradation rate of the buffer concentration, ionic strength and temperature have been investigated. The degradation kinetics were modeled with a non-linear least-squares curve-fitting program.

A general approach to the interpretation of pH buffer catalyzed degradation profiles

Abstract A general equation for the pH-dependent general acid-base catalyzed degradation profiles of polybasic weak electrolytes is presented. The potential information which can be deduced from such profiles is discussed. The method is illustrated with a hypothetical example.

Degradation kinetics of vincristine sulphate and vindesine sulphate in aqueous solutions

Abstract The degradation kinetics of the antineoplastic drugs, vincristine and vindesine, have been studied in the pH range from − 2 up to 11 at 80°C. A stability-indicating HPLC system with UV detection was utilized for the analysis of vincristine and vindesine in the reaction solutions. The influences of external factors (e.g. pH, buffer concentrations, ionic strength and temperature) on the degradation rate have been studied systematically. The relationship between pH and log k obs was modelled by using a non-linear least-squares curve-fitting computer program. From this plot thep K a values of vindesine have been calculated. This plot also showed that vincristine was most stable at pH 4.8 and vindesine at pH 1.9.

A general approach to the interpretation of pH degradation profiles in the presence of ligands

Abstract A general equation of pH-dependent degradation profiles of polybasic weak electrolytes in the presence of a ligand is presented. The potential information which can be deduced from such profiles is discussed. The method is graphically illustrated with a hypothetical example.