Solid-state study of mepivacaine hydrochloride.

Different crystalline forms of the local anaesthetic mepivacaine hydrochloride (MH) were revealed by Fourier transform infrared spectroscopy (FT-IR), not by conventional differential scanning calorimetry (DSC). The existence of two polymorphic anhydrous modifications was discovered and further characterized by X-ray powder diffraction and thermal analysis: Form II, the commercial one, and the more stable Form I, obtained by re-crystallization from Form II. Two pseudopolymorphs were also obtained: Form III, a solvate crystallized from ethanol and Form IV, a solvate crystallized from methanol. Single crystal X-ray diffraction data for both solvates were collected and their structures were determined. Form II, metastable and monotropically related to Form I, generates through desolvation of Form III, very often present in industrial processing, where crystallization from ethanol solution is a common practice. For the sake of clarity, the presence of polymorphic forms should be reported in the drug master files of MH. However, since MH is readily water soluble, the observed polymorphism has no relevance to its typical clinical use as aqueous solutions.

Improving gas chromatographic determination of residual solvents in pharmaceuticals by the combined use of headspace solid-phase microextraction and isotopic dilution.

Cyclohexane and toluene were gas chromatographically determined via headspace solid-phase microextraction both in ketoprofen drug substance and ketoprofen capsules by a procedure relying on isotopic dilution (ID), an analytical tool derived from mass spectrometry (MS). This approach, using an internal standard method, gave mean precision and accuracy (RSD 2.56%, 2.97% and bias 0.21%, -0.99% for cyclohexane and toluene, respectively) not obtainable by the more commonly used external standard ones in the presence of real sample matrices. Optimisation of the operative conditions was also supported by experimental design. More generally, the proposed method, exploiting ID without resort to the costly MS instrumentation, could be recommended whenever opportune deuterated analogues of the target analytes and GC capillary columns able to separate all the peaks involved are ready available on the market.

Development of a densitometric method for the determination of cephalexin as an alternative to the standard HPLC procedure.

A HPTLC-densitometric method was developed in order to obtain a reliable procedure for routine analysis of cephalexin in pharmaceutical formulations. Optimization of TLC conditions for the densitometric scanning was reached by eluting HPTLC silica gel plates in an horizontal developing chamber. Quantitation of cephalexin was performed in single beam reflectance mode by using a computer-controlled densitometric scanner and applying a five-point calibration. A linear regression has been found in the 200-1000 ng range. The setup method is precise, reproducible and accurate. Recovery was also assessed by comparison with the HPLC USP XXIII alternate method. In this case HPTLC-densitometry appears worth of consideration as being relatively inexpensive and time-saving (up to 12 samples can be determined simultaneously in less than 15 min with a solvent consumption of about 15 ml). The results suggest that the proposed method may be used in place of HPLC for the routine quantitation of cephalexin in both pure and dosage forms.

Evaluation of some benzyl and benzylidene monosubstituted gamma-butyrolactones and tetrahydrofurans as platelet activating factor antagonist agents.

Some benzyl and benzylidene monosubstituted gamma-butyrolactones and tetrahydrofurans were applied as platelet activating factor (PAF) antagonist agents. The results indicated that, whereas all benzyl derivatives are completely inactive, benzylidene substitution is the key feature for obtaining moderate activity. Molecular modeling and molecular electrostatic potential mapping are applied in conjunction with the most recent PAF-receptor model to rationalize the results.

Improvement of dissolution characteristics of psoralen by cyclodextrins complexation.

Psoralen was found to form an inclusion complex with beta-cyclodextrin (beta CD), heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta CD) and hepatakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM beta CD). Phase solubility studies revealed the formation of a 1:1 molar complexes. The stability constant were 663 M-1 for beta CD, 603 M-1 for DM beta CD and 69.6 M-1 for TM beta CD. The formation of complexes in the solid state was confirmed by spectroscopic analyses, X-ray diffractometry and differential thermal data. The solubility and dissolution rate of the complexed forms were improved, particularly for the DM beta CD complex. The strength of binding of psoralen to DNA was not influenced by complexation with cyclodextrins.

Investigation of mammalian lignan precursors in flax seed: first evidence of secoisolariciresinol diglucoside in two isomeric forms by liquid chromatograph/mass spectrometry.

A strong research effort has been devoted in recent years to the mammalian lignans enterolactone and enterodiol because of their claimed protective effects against breast and colon cancer. Some plant lignans appear to be precursors of these molecules. This paper reports a novel identification procedure for one of these precursors, the secoisolariciresinol diglucoside, in the extracts of defatted flax-seed meal. The procedure is based on high-performance liquid chromatography coupled with either ionspray or continuous-flow fast-atom bombardment mass spectrometry. The application of these techniques allowed the identification in flax seed of two isomeric forms of this precursor for the first time. The isomers are reasonable the two diastereoisomers, due to the two equivalent stereogenic centers present in the molecule.

Revealing the mammalian lignan precursor secoisolariciresinol diglucoside in flax seed by ionspray mass spectrometry.

Ionspray mass spectrometry allowed the rapid detection and unambiguous identification of secoisolariciresinol diglucoside, an important mammalian lignan precursor occurring in flax seed. It was observed that this compound is embedded in a complex form, probably a complex glucoside of still undisclosed structure, among the polar solvent extractables of flax seed from which it could not be released as such without the intervention of alkaline methanolysis. Comparison of ionspray mass spectra of untreated and methanolysed flax-seed extracts confirmed methanolysis as the crucial step in setting up any further analytical or preparative procedure concerned with secoisolariciresinol diglucoside.

Characterization of hematology lysing reagents containing quaternary ammonium halides using fast-atom bombardment mass spectrometry.

Positive- and negative-ion fast-atom bombardment (FAB) mass spectrometry has been employed to characterize pure dodecyl-, tetradecyl- and hexadecyl-trimethylammonium chlorides and bromides, compounds of high interest as lysing agents in hematologic analyses. In parallel, the same approach has been used for some commercially available lysing reagent products. While in positive-ion FAB mass spectra the presence of the abundant ions corresponding to the intact quaternary ammonium cations (Q+) is accompanied by the presence of [Q2X]+ (X = Cl, Br) species, in the negative-ion mode cluster ions such as [QX2]- are the sole ionic species that are easily evident. The mechanism for the formation of [Q2X]+ and [QX2]- species has been studied and some suggested explanations are given.

Characterization of Sanguinaria canadensis L. fluid extract by FAB mass spectrometry.

Positive-ion fast atom bombardment mass spectrometry was used for the rapid characterization of commercial Sanguinaria canadensis L. fluid extracts. Quaternary and non-quaternary benzophenanthridine alkaloids afford persistent peaks due to [M]+ and [M+H]+ ionic species, respectively, and their relative abundances are in good agreement with previously reported per cent analytical data. The procedure allowed sanguinarine, chelerythrine, chelirubine, sanguilutine, protopine, allocryptopine and the isomers sanguirubine and/or chelilutine to be effectively detected by means of persistent and intense peaks in all the samples examined.

Determination of benzalkonium chloride in contact lens solutions by positive-ion fast atom bombardment mass spectrometry.

Under positive-ion fast atom bombardment (FAB) mass spectrometric conditions, benzalkonium chloride (BAK) afforded intense peaks at m/z 304 and 332, corresponding to the intact cations [M--Cl]+ of C12 and C14 homologues, respectively. The use of benzethonium chloride as an internal standard and thioglycerol as a FAB matrix allowed the direct and specific determination of the BAK content (0.004-0.020%) in commercial hard contact lens solutions through the individual assay of the two alkyl homologues. A linear relationship between the homologue concentration and the peak-area ratio was observed over the concentration range 3-180 micrograms ml-1.