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.

Attention to metabolic hunger and its effects on Helicobacter pylori infection.

A significant decrease in the bacterial count of small intestinal mucosa has been observed in children with recurrent diarrhea or abdominal pain in the time that has elapsed from the previous meal. Humans may be trained to recognize metabolic feelings of hunger that are associated with a steady and slightly lower glycemia than baseline, between 4.7 and 3.9 mmol/L (intervention). An eating habit associated with a decrease in preprandial glycemia prevented diarrhea relapses, and was expected to impair intestinal microflora growth, including Helicobacter pylori in the stomach. The development of Helicobacter pylori infection might be prevented during childhood, and recovery from infection may be expected with intervention. The improvement in attention to metabolic feelings consisted of acquiring a predictive ability of glycemia by distinction between unsolicited hunger feelings (metabolic hunger) and those associated with external cues. Matching intake to the inbetween energy needs served to predict the subsequent emergence of the metabolic hunger. The matching was further compensated for the early or late emergence of metabolic hunger at the subsequent meals. Fruit and vegetables were increased to avoid abrupt glycemia lowering. This intervention was trained in 5-month periods. Subjects (209, 44, and 58) completed their training during 4-year periods between 1982 and 1994, and were enrolled in a prospective, controlled, randomized, interventional, preventive, and cohort study. The "prevention" hypothesis was tested in a subgroup of 86 healthy infants who were recalled in the years 1996 to 1998. A "recovery" study of approximately a 1-year intervention was investigated in 47 healthy subjects between ages 5 and 25, who were positive for anti-H. pylori and had no need for an immediate antibiotic treatment at entry. The following behavioral factors were recorded in a 7-day home diary and calculated: the fraction of meals induced by metabolic hunger out of 21 main mealtimes; average preprandial glycemia (DAP glycemia); daily intakes, activity; and bedtime hours. The decrease in preprandial glycemia was the objective measure of compliance with the recognition of "metabolic" hunger. Anthropometric measures and blood tests were obtained for nutritional and functional verifications. Average preprandial glycemia was 8.5 and 8.6% lower in the intervention groups than the control groups in the "prevention" and "recovery" studies, respectively, at the end of follow-up (p<0.05 and <0.001, respectively). A 4.7% seroprevalence of H. pylori infection was observed in the intervention group, with 30.2% in the control group at a mean age of 10 years after approximately an 8-year follow-up in the "prevention" study (p<0.0005). The seroprevalence decreased to 9 of 24 (37.5%) under intervention as opposed to 20 of 23 controls (87%) in the recovery study (p<0.002). A significant positive correlation was found between DAP glycemia and the anti-H. pylori serum antibody concentration (r = 0.52; p = 0.0002). A decrease in the level of immune stimulation by H. pylori infection was observed due to the intervention, which may have a preventive and therapeutic role on the infection.

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.

Direct quantitation of antiseptic quaternary ammonium compounds by fast atom bombardment mass spectrometry.

The medicinally important quaternary ammonium salts benzyldimethyltetradecylammonium chloride (BDTA), cetylpyridinium chloride and benzethonium chloride, all afford, under fast atom bombardment (FAB) mass spectrometric conditions, abundant and persistent [M-Cl]+ species usefully amenable to quantitative analysis with the aid of thioglycerol as a liquid FAB matrix. The use of BDTA as an internal standard allowed a direct, precise and accurate determination of cetylpyridinium and benzethonium chlorides, either as pure samples or in dosage forms, in the concentration range 0.05-2 mg/ml.

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.

Investigation of Pinus mugo essential oil oxygenated fraction by combined use of gas chromatography and dry column chromatography.

The oxygenated compounds of Pinus mugo Turra essential oil were investigated by a combination of GC and dry column chromatography (DCC) coordinated by GC data processing. The collected data resulted in a bar graph ("normalized" gas chromatogram) giving the RRT's and relative amounts of 68 components; 38 of them were identified by MS and IR. The described procedure may be used for essential oil analysis in general.

Same growth and different energy intake over four years in children suffering from chronic non-specific diarrhoea.

An increase in energy intake often occurs at weaning and this may depend on the current practice of offering energy-dense foods ad libitum. In two-year-old lean infants suffering from chronic non-specific diarrhoea (CNSD), the offering of food was evaluated by caregivers at every meal on the basis of food need expressions and non-starchy vegetable acceptance, taking into account the maintenance of good temper and normal activity between meals. The purpose was to avoid diarrhoea recurrence. This form of regulation was continued in a prospective, controlled, randomized investigation to explore: (i) familial pre-determination of growth and (ii) the existence of an 'unnecessary' fraction of energy intake, i.e. a fraction which may habitually be excluded while still maintaining the same normal intermeal behaviour, intellectual and physical achievements, growth, skinfold thicknesses and blood parameters. Seven-day intake home diaries and clinical assessments were performed every 6 to 12 months. Growth records were investigated in siblings. Eighty-two of 91 experimental subjects and 32 of 41 randomized ones in the control group were followed for up to four years. The control group maintained a significantly higher (15-30%) energy intake than the experimental children, without any fattening or growth acceleration, or any improved results in inter-meal behaviour, intellectual and physical achievements or blood parameters for four years. The normal median weight was reached in the experimental and control children in the sixth year of life and in the siblings in the fourth year of life.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Determination of isosorbide-5-mononitrate in tablets by differential pulse polarography.

A differential pulse polarographic method requiring little sample separation was developed for the determination of isosorbide-5-mononitrate in tablet dosage form with the standard addition technique and without interference from common excipients. Britton-Welford buffer (pH 3.0) was used as the supporting electrolyte, the single peak occurring at -0.36 V vs. a reference Ag/AgCl electrode. The irreversible, diffusion controlled, two-electron reduction process at the dropping mercury electrode permits a precise and accurate determination of the active ingredient in the 0.4-20 microgram/ml concentration range.

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.