Analysis of nonhuman N-glycans as the minor constituents in recombinant monoclonal antibody pharmaceuticals.

Minor N-linked glycans containing N-glycolylneuraminic acid residues and/or α-Gal epitopes (i.e., galactose-α1,3-galactose residues) have been reported to be present in recombinant monoclonal antibody (mAb) therapeutics.

Charge heterogeneity of a therapeutic monoclonal antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin.

A robust and highly reproducible capillary isoelectric focusing (cIEF) method for the evaluation of charge heterogeneity of monoclonal antibody (mAb) pharmaceutical which contains covalently bound antitumor compounds was developed using a combination of commercially available dimethylpolysiloxane-coated capillary and carrier ampholyte. In order to optimize major analytical parameters for robust mobilization, experimental responses from three pI markers were selected. The optimized method gave excellent repeatability and intermediate precision in estimated pI values of charge variants with relative standard deviations (RSDs) of not more than 0.

[Simple method for quantitative determination of active polymorphous and amorphous drugs in drug products by fourier transform-Raman spectroscopy].

The feasibility of a simple Fourier transform (FT)-Raman spectroscopic method for the quantitative determination of unexpected active drug polymorphs or amorphous in drug products was explored. In this study, calibration samples were prepared by physically mixing drug substances with their polymorphs or amorphous, without using excipients. A partial least-squares (PLS) method was applied to the quantitative analysis of the FT-Raman spectra obtained.

Characterization of pharmaceutical polymorphs by isothermal calorimetry.

A great number of pharmaceutical substances exist in crystalline solid-state. Because of the complexity of their chemical structure many different polymorphs of a given substance can exist. Polymorphic forms of solid pharmaceuticals influence not only their dissolution behavior, i.

Matrix media selection for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography.

The influence of the matrix medium used for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography was investigated. The purpose of this paper is to propose a guide for the choice of a matrix medium suitable for the determination of residual solvents of interest. Dimethylsulfoxide (DMSO), N,N-dimethyformamide (DMF), N,N-dimethylacetamide (DMA), benzyl alcohol (BA), 1,3-dimethyl-2-imidazolidinone (DMI) and water were studied as matrix media, and seventeen solvents used for the synthesis and purification of drug substances were used as target analytes.

A kinetic and thermodynamic study of seratrodast polymorphic transition by isothermal microcalorimetry.

The development of isothermal microcalorimetry to a study of the kinetic and thermodynamics of polymorphic transitions in seratrodast ((+/-)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid) Form II is reported. Sieved samples of Form II were allowed to convert to Form I, in a reaction vessel of an isothermal microcalorimeter, under 13, 31, 63 and 93% relative humidity (RH) between 48 and 65 degrees C. The power (Phi, in Watts) versus time curves from the microcalorimeter were integrated into the heat output (q, in Joules) versus time curves to yield fractional extent of Form I converted versus time curves.

A novel method for estimation of transition temperature for polymorphic pairs in pharmaceuticals using heat of solution and solubility data.

A novel method for thermodynamic stability studies of polymorphic drug substances has been developed. In order to estimate the transition temperature for an enantiotropic polymorphic pair, a formula for calculating the temperature at which the solubilities of each polymorph become equal has been derived with heat of solution and solubility as the variables. This formula is based on the assumption that van't Hoff plots (logarithmic solubility versus reciprocal of absolute temperature plots) of each polymorph show a straight line (heat of solution is independent of temperature) whose slope can be expressed as a function of heat of solution.