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Enantioseparation of the novel antidepressant mirtazapine and its active demethyl metabolite by means of HPCE
Mirtazapine (1,2,3,4,10,14b-hexahydro-2-methyl-pyrazino[2,1-a]-pyrido[2,3-c][2-benzazepine]), is the first noradrenergic and specific serotonergic antidepressant ('NaSSA'), that was approved by the Food and Drug Administration for the treatment of depression in June 1997. It is administered clinically as Remeron®, a 50:50 mixture of S(+) and R(-) enantiomers, that is supplied for oral administration as scored film-coated tablets containing 15 or 30 mg of mirtazapine.
It has two major metabolites, N-demethylmirtazapine and 8-hydroxymirtazapine. The parent compound demonstrates the major pharmacological activity. Some minor activity is shown by the demethyl metabolite while the hydroxy metabolite is not pharmacologically active. The receptor binding affinities of the enantiomers of mirtazapine are different, the (+) enantiomer being the more potent adrenoceptor antagonist of the two. For this reason a chiral separation of the enantiomers may be important in pharmacokinetic studies and for evaluating the clinical response.
Aim of this study is the development of a capillary electrophoretic method for the enantioseparation of mirtazapine and its active metabolite. For method optimisation several parameters were investigated, such as cyclodextrin and buffer concentration, buffer pH and capillary temperature. Baseline enantioseparation of the racemic compounds was achieved in 2.5 minutes using a fused silica capillary (50 μm I.D. and 48.5, 40.0 cm, total and effective length, respectively), filled with a background electrolyte consisting of a 50 mM phosphate buffer at pH 2.5 supplemented with 0.3% (w/v) carboxymethyl-beta-cyclodextrin sulfate at 12.5°C and applying a voltage of 20 kV. UV detection was set at 205 nm.
The implemented fast CZE stereoselective separation of mirtazapine has been applied for the determination of the enantiomeric purity of preparats containing racemic mirtazapine. The extraction of mirtazapine from the tablets consisted of a simple one-step dissolution with methanol, centrifugation and dilution. The electrophoretic procedure demonstrated to be very rapid and feasible and seems to be suitable for quality control of mirtazapine tablets. Experiments are in progress in order to apply the method to the determination of mirtazapine and its active metabolite in biological fluids
Separation of catechins and methylxanthines in tea samples by capillary electrochromatography
In this paper, the simultaneous separation of several polyphenols such as (+)-catechin, ( – )-epicatechin, ( – )-epigallocatechin, theophylline, caffeine in green and black teas by capillary electrochromatography (CEC) was developed. Several experimental parameters such as stationary phase type, mobile phase composition, buffer and pH, inner diameter of the columns, sample injection, were evaluated to obtain the complete separation of the analysed compounds. Baseline resolution of the studied polyphenols was achieved within 30 min by using a capillary column (id 100 lm) packed with bidentate C18 particles for 24.5 cm and a mobile phase composed of 5 mM ammonium acetate buffer pH 4 with H2O/ACN (80:20, v/v). The applied voltage and the temperature were set at 30 kV and 208C. Precision, detection and quantification limits, linearity, and accuracy were investigated. A good linearity (R2 A 0.9992) was achieved over a concentration working range of 2 – 100 lg/mL for all the analytes. LOD and LOQ were 1 and 2 lg/mL, respectively, for all studied compounds.
The CEC method was applied to the analysis of those polyphenols in green and black tea samples after an extraction procedure. Good recovery data from accuracy studies ranged between 90% and 112% for all analytes
MANDIBLE BROWN TUMOR CAUSED BY PRIMARY HYPERPARATHYROIDISM
Brown tumor is a uni or multi-focal bone lesion, which represents the terminal stage of the hyperparathyroidism-dependent bone pathology. It often appears as an expansive osteolytic lesion of the bone, commonly in the mandible, ribs, pelvis and femur. A 56 year-old male patient presented with an asymptomatic unilocular radiolucent lesion of the right mandible without teeth. The lesion had a diameter of about 3 cm, had sharply delimited margins and was surrounded by an osteosclerotic rim. Under local anesthesia, the lesion was extracted surgically. The microscopic diagnosis was brown tumor of the mandible. The following report describes a patient with secondary hyperparathyroidism who developed a brown tumor of the mandible, discuss the differential diagnosis, and review the literatur
The importance of immediately loaded immediate post-extractive implants in esthetical rehabilitation: case series.
The aim of this paper was to estimate, in a retrospective way, integration of hard and soft tissues in immediately loaded immediate postextractive implants. Benefits of this technique could be: single stage surgery, biological saving of tissues, aesthetic management of edentulism, good integration of both hard and soft tissues. Immediate loading of a postextractive implant seems also to produce a positive effect on the quality of perimplant soft tissues. The implants used in the present study have some advantages such as high auto-threading and auto-tapping ability, progressive increase of the thickness of the threads, at the apical and coronal level. All these features have helped to obtain a high primary stability
Micellar electrokinetic chromatography for determination of drug partition in phospholipids
The lipophilicity of pipemidic, nalidixic and oxolinic acids was determined by forming phospholipidic micelles directly in an electrophoretic capillary. Phosphatidylcholine derivatives, namely L-alpha-dilauroyl phosphatidylcholine (DLPC) or L-alpha-dimiristoyl phosphatidylcholine (DMPC), were added in the run buffer (50 mM phosphate buffer at pH 7.4). To obtain a mixed micelle, phospholipidic derivatives and sodium cholate were together added in the run buffer. Considering the increasing of migration time when phosphatidylcholine derivative is added in the run buffer, Ks can be determined and then quinolones lipophilicity
Evaluation of teicoplanin chiral stationary phases of 3.5 and 5 um inside diameter silica microparticles by polar-organic mode capillary electrochromatography
Different types of fused-silica capillaries of 75 um inside diameter (ID) were packed, namely type A and B, and evaluated for the direct resolution of racemates of several basic compounds by enantioselective capillary electrochromatography (e-CEC). Type
A was packed with a chiral stationary phase (CSP) containing teicoplanin (TE) mixed with silica microparticles (3:1 w/w) while type B contained only the TE-CSP. In both cases, particles of different sizes (3.5 and 5 um ID) were employed. A polar-organic
mobile phase containing methanol-acetonitrile (60–40% v/v and 0.05% w/v ammonium acetate was used. Several b-blockers (alprenolol, oxprenolol, metoprolol, pindolol, salbutamol, propranolol, atenolol, acebutolol) were baseline-enantioresolved with both capillary types, in very short times
Danni parodontali iatrogeni da pratiche conservative, protesiche, ortodontiche. Necessità di una sempre più fattiva collaborazione inter-disciplinare.
THERMODYNAMIC BEHAVIOR OF SOME ELECTROLYTES IN ETHANE-1,2-DIOL FROM-10 TO +80-DEGREES-C
Conductivities of the electrolytes NaBr, NaPi, HPi, NaBPh4, and Ph4PBr in ethane- 1, 2-diol were determined in the - 10 less-than-or-equal-to t less-than-or-equal-to + 80-degrees-C temperature range. The experimental data were analyzed by the Fuoss-Hsia equation, which provides further informative parameters such as the dissociation constant (K) of the ion pairs formed in solution, the limiting equivalent conductivity (LAMBDA0), and the ion-size parameter (a). Thermodynamic behaviour of these electrolytes was derived from analysis of the K values. Single-ion conductivities were evaluated on the basis of the assumption of Ph4PBPh4 as reference electrolyte
WELDING IMPROVES THE SUCCESS RATE OF ONE-PIECE IMPLANTS
One-piece implants incorporate the trans-mucosal abutment as an integral part of the implant. One-piece implant are usually welded together and immediately loaded. Since few reports are available on the effect of welding on implant’ survival, a retrospective study is performed.
Nineteen patients (10 females and 9 males) with a median age of 62 years (min-max 43-80) were enrolled. The mean follow-up was 7 months. A total of 176 one-piece implants (Diamond, BIOIMPLANT, Milan, Italy) were inserted. One hundred and thirty-eight implants were welded. Disease-specific survival curves were calculated according to the product-limit method.
In our series SVR is 93.75. Kaplan-Meier algorithm demonstrated that welded implants have a statistical significant better survival than unwelded implants.
In conclusion one-piece implants are reliable devices for oral rehabilitation (since they have a SVR = 93.75) and welding procedure reduce the number of lost implant
Chiral separations by capillary zone electrophoresis with the use of cyanoethylated-a-cyclodextrin as chiral selector”
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