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Accurate mass measurements are used to determine the elemental composition and formulae of molecules to confirm their identity or to assist in their characterization. Currently, the most widely used techniques for measuring exact masses employ magnetic sector instruments, Fourier transform ion cyclotron resonance mass spectrometers and lower resolution instruments such as time-of-flight (TOF) and quadrupole-TOF. This paper reports the accurate mass measurement using a triple quadrupole mass spectrometer. Indeed, the recently introduced triple quadrupole mass spectrometer, with unique enhanced mass-resolution capability, has demonstrated simple data acquisition methods and requires few experiments to measure exact masses with accuracy and determines elemental compositions of both protonated and deprotonated molecules. All the accurate mass measurements were performed using both positive and negative electrospray ionization in enhanced mass-resolution mode (peak width of 0.1 Th FWMH). Several new drug entities were investigated as simulated unknowns and analyzed by means of an accurate mass liquid chromatography/electrospray ionization mass spectrometry (AM-LC/ESI-MS) method. The accurate mass measurements resulted in only one proposed elemental composition for all tested compounds, using reasonable elemental limits and mass tolerance for the calculation. Moreover, all the experimentally determined accurate mass measurements gave satisfactory results in terms of accuracy (lower than 5 ppm)., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

A very highly sensitive and highly selective liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed to evaluate and quantify a new drug candidate in different biological matrices. Following a simple plasma protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a new generation of triple-quadrupole mass spectrometer. The recently introduced triple-quadrupole mass spectrometer, the TSQ Quantum Ultra, with enhanced mass-resolution capability, demonstrated improved sensitivity (0.05 ng/mL), coupled with suitable accuracy and precision, over a broad linear dynamic range (0.05-1000 ng/mL). A comparison of the assay performance data (dynamic range, calibration curve equation, precision and accuracy) of the enhanced resolution method against a unit resolution method under optimized conditions showed the performance improvement of the enhanced mass resolution method for bioanalytical high-throughput applications. The enhanced mass resolution method herein described was successfully applied to the evaluation of the pharmacokinetic profile of a new drug candidate in rat, rabbit and dog plasma samples., (Copyright 2006 John Wiley & Sons, Ltd.)

An overview of the electrokinetic chromatographic methods for the analysis of antiepileptic drug levels in biological samples is presented. In particular, micellar electrokinetic capillary chromatography is a very suitable method for the determination of these drugs, because it allows a rapid, selective, and accurate analysis. In addition to the electrokinetic chromatographic studies on the determination of antiepileptic drugs, some information regarding sample pretreatment will also be reported: this is a critical step when the analysis of biological fluids is concerned. The electrokinetic chromatographic methods for the determination of recent antiepileptic drugs (e.g., lamotrigine, levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin, ethosuximide, valproic acid) will be discussed in depth, and their pharmacological profiles will be briefly described as well.

A reliable micellar electrokinetic capillary chromatographic method was developed and validated for the determination of lamotrigine and its metabolites in human plasma and urine. The variation of different parameters, such as pH of the background electrolyte (BGE) and Sodium dodecyl sulfate (SDS) concentration, were evaluated in order to find optimal conditions. Best separation of the analytes was achieved using a BGE composed of 10 mM borate and 50 mM SDS, pH 9.5; melatonin was selected as the internal standard. Isolation of lamotrigine and its metabolites from plasma and urine was accomplished with an original solid-phase extraction procedure using hydrophilic-lypophilic balance cartridges. Good absolute recovery data and satisfactory precision values were obtained. The calibration plots for lamotrigine and its metabolites were linear over the 1-20 microg/mL concentration range. Sensitivity was satisfactory; the limits of detection and quantitation of lamotrigine were 500 ng/mL and 1 microg/mL, respectively. The application of the method to real plasma samples from epileptic patients under therapy with lamotrigine gave good results in terms of accuracy and selectivity, and in agreement with those obtained with an high-performance liquid chromatography (HPLC) method.

A high-throughput liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) assay using automated sample preparation has been developed for the determination of valproic acid (VPA) in mouse plasma. A liquid-handling system was programmed to prepare calibration standard solutions in plasma, as well as quality controls and clinical samples. Plasma protein precipitation was performed on a 96-well plate, and the collected supernatant was directly injected into a reversed-phase LC/ESI-MS/MS system in the negative ionization mode. The calibration curve for VPA was linear over a dynamic range of 0.15-100 microg/mL. The limit of detection was 75 ng/mL and the lower limit of quantitation was 150 ng/mL. Intra- and inter-day validation assays of the semi-automated plasma analysis showed satisfactory accuracy and precision., (2005 John Wiley & Sons, Ltd.)

Polymeric micelles based on polyvinyl alcohol substituted with oleic acid were used as vehicles for progesterone and folic acid. The ability of this amphiphilic polymer to entrap lipophilic drugs and to generate stable micelles in aqueous neutral medium makes it a good candidate for drug delivery. The release of the loaded drugs in acidic environments represents another important property of these systems. Size of micelles, their stability, and their drug-loading capacity were evaluated, as well as the in vitro controlled-release profiles at pH 7.4 and 5.5.

Mirtazapine is a recent noradrenergic and specific serotonergic antidepressant drug. A capillary electrophoretic method has been developed for the enantioseparation and analysis of mirtazapine and its main active metabolite, N-desmethylmirtazapine, in human plasma. For method optimisation several experimental parameters were investigated, such as type and concentration of the chiral selector, buffer pH and capillary temperature. Baseline enantioseparation of the analytes was achieved in 2.5 min in a fused silica capillary (50 microm i.d.; 48.5 cm total length; 8.5 cm effective length) using carboxymethyl-beta-cyclodextrin, dissolved in a background electrolyte consisting of 50 mM phosphate buffer at pH 2.5, as the chiral selector. UV detection was set at 205 nm. A careful pre-treatment of plasma samples was developed, using solid-phase extraction with hydrophilic-lipophilic balance cartridges (60 mg, 3 mL), eluting the sample with methanol, then concentrating it 37.5 times before injection. Extraction yield values are very satisfactory, being the average 89% for mirtazapine and 73% for N-desmethylmirtazapine. Application of the method to some human plasma samples has given satisfactory results.

Stationary phases for capillary electrochromatography with a longitudinal gradient of functionalities have been prepared via photoinitiated grafting of polymer chains onto the pore surface of a porous polymer monolith. In order to achieve the desired retention and electroosmotic flow, the hydrophobic poly(butyl methacrylate-co-ethylene dimethacrylate) monolith with optimized porous properties was grafted with a layer of ionizable polymer, poly(2-acrylamido-2-methyl-1-propanesulfonic acid). A moving shutter and a neutral density filter were used to control the dose of UV light received at different locations along the monolith in order to create the longitudinal gradient of functionalities. Formation of the desired gradients was confirmed using electron probe microanalysis of different locations along the column. The preparation technique significantly affects performance in the CEC mode as demonstrated on the separations of a model mixture using columns both with homogeneous distribution of grafts and with a gradient of functionality. Columns grafted with the gradient of functionalities were found superior to those functionalized uniformly. A comparison of the performance of the gradient column with another containing evenly distributed functionalities showed the performance benefits of the "gradient" column.

The development of new "atypical" antipsychotic agents, which are safer than classical neuroleptics and also active against the negative symptoms and neurocognitive deficits caused by the illness, has produced a significant advancement in the treatment of schizophrenia. The atypical (or "second generation") antipsychotics have several therapeutical properties in common, however they can significantly differ with regard to clinical potency and side effects. The main features regarding pharmacodynamics, pharmacokinetics and pharmacological interactions of the most important atypical antipsychotics, namely clozapine, olanzapine, quetiapine and risperidone, are treated herein. Several analytical methods available for the therapeutic drug monitoring of these drugs are also presented, as well as the novel formulations, which can notably improve the therapy of schizophrenia. Other very recent atypical agents, such as ziprasidone, aripiprazole, iloperidone, sertindole and zotepine will also be briefly described.

The separation and simultaneous determination of caffeine, paracetamol, and acetylsalicylic acid in two analgesic tablet formulations was investigated by capillary electrochromatography (CEC). The effect of mobile phase composition on the separation and peak efficiency of the three analytes was studied and evaluated; in particular, the influence of buffer type, buffer pH, and acetonitrile content of the mobile phase was investigated. The analyses were carried out under optimized separation conditions, using a full-packed silica capillary (75 microm ID; 30.0 cm and 21.5 cm total and effective lengths, respectively) with a 5 microm C8 stationary phase. A mixture of 25 mM ammonium formate at pH 3.0 and acetonitrile (30:70 v/v) was used as the mobile phase. UV detection was at 210 nm. Good linearity was found in the range of 50-200, 20-160, and 4-20 microg/mL for acetylsalicylic acid (r2=0.9988), paracetamol (r2=0.9990) and caffeine (r2=0.9990), respectively. Intermediate precision (RSD interday) as low as 0.1-0.8% was found for retention times, while the RSD values for the peak area ratios (Aanalyte/AIS) were in the range of 1.9-2.9%. The optimized CEC method was applied to the analysis of the studied compounds present in commercial tablets.

An accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of the novel antiepileptic, Levetiracetam, has been developed. Three clean-up procedures for the analysis of Levetiracetam in human plasma were implemented and evaluated, namely solid-phase extraction, deproteinization by addition of organic solvents and formation of insoluble salts. Adenosine was used as the internal standard for all three sample pretreatment procedures. Among the several cartridges used for solid-phase extraction, the hydrophilic-lypophilic balance (Oasis) HLB) phase provides the best extraction yield of Levetiracetam, together with high precision. With the two other clean-up procedures involving plasma deproteinization by addition of methanol or zinc sulphate, lower sensitivity and precision of the assays were obtained. However, they are cheaper and faster when compared with the solid-phase extraction procedure., (Copyright 2003 John Wiley & Sons, Ltd.)

Quetiapine (bis [2-(2-[4-(dibenzo[b,f][1,4]thiazepin-11-yl]ethoxy)ethanol]fumarate) is the most recent agent introduced on the drug market for the treatment of psychotic disorders. Two different analytical methods for the quality control of quetiapine in commercial formulations have been developed and compared: a spectrophotometric method and a capillary zone electrophoretic (CZE) method. The spectrophotometric assay was carried out measuring the absorbance at a wavelength of 246 nm. The CZE method used an uncoated fused-silica capillary and a pH 2.5, 50 mM phosphate buffer as the background electrolyte. The detection wavelength was 205 nm, the separation voltage was 15 kV, and a complete electrophoretic run lasts less than 2.5 min. Extraction of quetiapine from the commercial tablets consisted of a simple one-step treatment with a pH 2.5, 50 mM phosphate buffer. Linearity was observed in the 5-25 microg ml(-1) concentration range of quetiapine for the spectrophotometric method, and in the 5-50 microg ml(-1) concentration range for the electrophoretic method. Both methods gave satisfactory results in terms of repeatability and intermediate precision (RSD<1.9%). Also accuracy values were very good for both methods, the recovery being between 98.2 and 100.5%.

A simple and fast capillary electrophoretic method has been developed for the enantioselective separation of citalopram and its main metabolites, namely N-desmethylcitalopram and N,N-didesmethylcitalopram, using beta-cyclodextrin (beta-CD) sulfate as the chiral selector. For method optimisation several parameters were investigated, such as CD and buffer concentration, buffer pH, and capillary temperature. Baseline enantioseparation of the racemic compounds was achieved in less than 6 min using a fused-silica capillary, filled with a background electrolyte consisting of a 35 mM phosphate buffer at pH 2.5 supplemented with 1% w/v beta-CD sulfate and 0.05% w/v beta-CD at 25 degrees C and applying a voltage of -20 kV. A fast separation method for citalopram was also optimized and applied to the analysis of pharmaceutical formulations. Racemic citalopram was resolved in its enantiomers in less than 1.5 min using short-end injection (8.5 cm, effective length) running the experiments in a background electrolyte composed of a 25 mM citrate buffer at pH 5.5 and 0.04% w/v beta-CD sulfate at a temperature of 10 degrees C.

A simple and highly sensitive high-performance liquid chromatographic (HPLC) method for the simultaneous determination of cis(Z)-clopenthixol and trans(E)-clopenthixol in human plasma has been developed. The chromatographic analysis was carried out isocratically on a reversed-phase column (C(8) 150 x 4.6 mm I.D., 5 microm) using a mixture of 25 mM phosphate buffer and acetonitrile (65:35 v/v, pH* 3.0) as the mobile phase, and ultraviolet detection at 230 nm. Plasma sample pretreatment was accomplished by means of an original solid-phase extraction (SPE) procedure carried out on cyanopropyl cartridges, with a high extraction yield and good selectivity. Under the optimum conditions, calibration graphs of spiked human plasma samples were obtained over the concentration ranges 1-300 ng ml(-1) for cis(Z)-clopenthixol and 1-200 ng ml(-1) for trans(E)-clopenthixol. The limit of detection (LOD) was 0.3 ng ml(-1) for both cis(Z)- and trans(E)-isomers of clopenthixol. The method was successfully applied to the determination of cis(Z)-clopenthixol and trans(E)-clopenthixol in plasma samples of schizophrenic patients undergoing therapy with zuclopenthixol.

Background and Objective: Patients affected by glaucoma refractory to medical or surgical treatment are difficult to treat. The aim of this study was to evaluate the long-term effect of contact transscleral diode laser cyclophotocoagulation (DLPC) on intraocular pressure (IOP) and on visual acuity of these patients., Patients and Methods: One hundred and twenty eyes of 107 patients suffering from refractory glaucoma and treated with DLPC were followed at the Eye Clinic of Verona University for an average of 26 +/- 8 months. Mean age was 57 +/- 26 years. IOP, visual acuity, and ocular complications were analyzed., Results: A total of 207 treatments were given. More than one treatment was given in 55 eyes (45.8%). Mean pretreatment IOP was 30.4 +/- 3.1 mm Hg. At the last follow-up, mean IOP was 20.3 +/- 1.8 mm Hg. Mean total medications were reduced from 4.5 +/- 0.5 to 2.3 +/- 0.3. No serious complications occurred in the 207 treatments. Visual acuity remained stable in 66 eyes (55%), improved in 25 eyes (20.8%), and decreased in 29 eyes (24.2%)., Conclusions: DLPC was effective in lowering IOP in eyes with refractory glaucoma. It also served to reduce the number of antiglaucoma medications, thus improving both the quality of life of the patients and their compliance to therapy. This procedure is relatively safe, very fast and easy to learn. However, careful attention is required to determine the exact position of the ciliary body in malformative glaucoma. Multiple treatments may be required to control IOP., (Copyright 2003 S. Karger AG, Basel)

A reliable micellar electrokinetic chromatographic method for the determination of oxcarbazepine and its two main metabolites, 10-hydroxycarbamazepine and 10,11-trans-dihydroxy-10,11-dihydroxycarbamazepine, in human plasma was developed. The separation and determination of the analytes was achieved using a system consisting of 60 mM SDS in phosphate buffer (30 mM, pH 8.0), to which 20% (v/v) methanol was added. Separation was carried out in an uncoated fused-silica capillary with a separation voltage of 25 kV and currents typically less than 40 microA. Spectrophotometric detection was at 205 nm. Isolation of oxcarbazepine and its metabolites from plasma was accomplished by a solid-phase extraction procedure. The mean extraction yield of the analytes from plasma was higher than 94%. The linear correlation coefficients were better than 0.994 for all analytes. The limit of detection was 0.05 microg/mL, the limit of quantitation 0.15 microg/mL. The repeatability for the spiked blank plasma samples was lower than 1.9% and the intermediate precision lower than 2.1%, both expressed as RSD%. The results obtained analysing real plasma samples from epileptic patients under therapy with Tolep were satisfactory in terms of precision, accuracy and detectability., (Copyright 2003 John Wiley & Sons, Ltd.)

A rapid capillary zone electrophoresis method with indirect UV detection was developed and validated for the determination of valproic acid (VPA) in human plasma. The analyses were carried out under optimized conditions, using a buffer system composed of 15 mM benzoate and 0.5 mM cetyltrimethylammonium bromide at pH 6.0, and 25% v/v methanol; 2-hydroxybutyric acid was selected as the internal standard (IS). The capillary electrophoresis (CE) separation was carried out at a negative potential of 30 kV and the indirect UV detection was operated at 210 +/- 20 nm for all assays. The influence of buffer pH, ionic strength, concentration of electroosmotic flow (EOF) modifier and organic modifier on indirect signal response and migration behavior of the organic acid was investigated. Isolation of VPA from plasma was accomplished by a carefully implemented procedure using methanol as the precipitant agent. Using a high ratio of methanol to plasma for deproteinization (4:1), good absolute recovery of the analyte and satisfactory selectivity was obtained. The calibration line for VPA was linear over the 1-100 microg/mL concentration range. Sensitivity was high; in fact, the limit of detection (LOD) of VPA was 150 ng/mL and 450 ng/mL the limit of quantitation (LOQ). The results obtained analyzing real plasma samples from schizophrenic patients under polytherapy with VPA as well as antipsychotic drugs were satisfactory in terms of precision, accuracy and sensitivity.

Progesterone was determined in commercial pharmaceutical formulations and experimental micellar systems by means of two analytical methods based on liquid chromatography and derivative spectrophotometry. The chromatographic analysis, with ultraviolet detection at 245 nm, was carried out on a C8 column using a mobile phase composed of 2-propanol and a pH 2.5, 30 mM phosphate buffer. Derivative spectrophotometry (DS) used the difference between the values of the first derivative at 227.2 and 253.6 nm. Both methods require only a simple extraction procedure of progesterone from the formulations before analysis. The high-performance liquid chromatography (HPLC) procedure allows for the quantitative determination of progesterone in all pharmaceutical formulations tested (oily and alcoholic injectable solutions, gel preparations and soft capsules) and also of the newly-developed polymeric micellar system. On the contrary, the derivative spectrophotometric method is not suitable for the pharmaceutical formulation containing estradiol and for the new micellar systems. The results obtained with the two methods are in good agreement and always satisfactory in terms of precision and accuracy.

Two different analytical methods for the quality control of fluoxetine in commercial formulations have been developed and compared: a spectrofluorimetric method and a capillary zone electrophoretic (CZE) method. The fluorescence emission values were measured at lambda=293 nm when exciting at lambda=230 nm. The CZE method used an uncoated fused-silica capillary and pH 2.5 phosphate buffer as the background electrolyte. The extraction of fluoxetine from the capsules consisted of a simple one-step dissolution with methanol/water, filtration and dilution. Both methods gave satisfactory results in terms of precision; the best results were obtained for the electrophoretic method, with RSD% values always lower than 2.0%. The accuracy was assessed by means of recovery studies, which gave very good results, between 97.5 and 102.6%. Furthermore, both methods also have the advantage of being very rapid.

The amount of melatonin in galenic tablets was determined by means of two feasible and accurate analytical methods. The high performance liquid chromatography (HPLC) with ultraviolet detection at 223 nm used a C(18) reversed-phase column; the linear scan voltammetric procedure (LSV) employs a pH 3.0 phosphate buffer as the supporting electrolyte for the oxidation process of melatonin, which has a current intensity maximum at +850 mV. The two methods gave satisfactory results in terms of precision and accuracy. In fact, the data of repeatability and intermediate precision expressed as percentage relative standard deviations (RSD%) were < or =2.8 and the accuracy values, resulting from recovery experiments, were between 99.0 and 101.3%. Both methods are suitable for quality control of melatonin in galenic preparations; the LSV procedure is more rapid, the HPLC method is more sensitive and more precise.

A rapid and feasible method was developed for the analysis of carbamazepine and its five metabolites (10,11-dihydro-10,11-epoxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, 10,11-dihydro-10-hydroxycarbamazepine, 2-hydroxycarbamazepine and 3-hydroxycarbamazepine) in human plasma. Separation of the analytes is based on micellar electrokinetic chromatography, in untreated fused-silica capillary (48.5/40.0 cm length, 50 microm I.D.) with phosphate buffer (30 mM, pH 8.00) as background electrolyte, containing 50 mM sodium dodecylsulfate, and methanol (15%, v/v) as organic modifier. Clean up of human plasma samples was carried out by means of a solid-phase extraction procedure, which gave a high extraction yield for all six carbamazepines (>88%). The overall precision of the method gives a mean RSD of about 1.8%. The limit of quantitation for all analytes is < or = 0.30 microg ml(-1), the limit of detection < or = 0.12 microg ml(-1).

Background and Objective: Patients with glaucoma refractory to medical or surgical treatment are difficult to treat. The aim of this study was to evaluate the effect of contact transscleral diode laser cyclophotocoagulation (DLPC) on these patients' intra-ocular pressure (IOP) and visual acuity., Patients and Methods: 37 eyes of 36 patients who suffered from refractory glaucoma and who had undergone DLPC, were followed at the Eye Clinic of Verona University for an average of 14 +/- 4 months. The average age was 54 +/- 26 years. IOP, visual acuity and ocular complications were analysed., Results: A total of 71 treatments were given. More than 1 treatment was given in 22 eyes (59%). The mean pretreatment IOP was 33.1 +/- 3.3 mm Hg. At the last follow-up, the mean IOP was 21 +/- 1.6 mm Hg. Mean total medications were reduced from 4.4 +/- 0.5 to 2.4 +/- 0.3. No serious complications occurred in 71 treatments. Visual acuity remained stable in 25 eyes (67.5%), improved in 6 eyes (16.2%) and decreased in 6 eyes (16.2%)., Conclusions: DLPC is effective in lowering IOP in eyes with refractory glaucoma. It also serves to reduce the number of antiglaucoma medications. This procedure is relatively safe. Nevertheless, multiple DLPC applications may be needed., (Copyright 2001 S. Karger AG, Basel)

Purpose: To assess phacoemulsification and posterior chamber intraocular lens (IOL) implantation as an effective, safe, and predictable technique for the correction of high myopia., Setting: University Eye Clinic of Verona, Verona, Italy., Methods: A series of 25 eyes with myopia higher than -12.0 diopters (D) had clear lens extraction by phacoemulsification and IOL implantation in the capsular bag. The mean postoperative follow-up was 42.92 months +/- 3.76 (SD)., Results: No serious intraoperative complications occurred. Uncorrected visual acuity improved in all cases. The mean postoperative best corrected visual acuity improved by an average of 1 line. One case (4.0%) of postoperative retinal detachment (RD) occurred at 12 months. One case (4.0%) of biometric error (3.0 D) occurred., Conclusion: Clear lens extraction by phacoemulsification and IOL implantation in a series of highly myopic eyes was effective and had an acceptable predictability and a low rate of complications. Careful evaluation of the retinal periphery by indirect ophthalmoscopy is recommended to avoid postoperative RD.

The concentrations of vitamin A, beta-carotene, and all-trans-retinoic acid in oral preparations were determined in a single analysis by a method based on isocratic, reversed-phase liquid chromatography (LC). The LC system consisted of a C18 column, a mobile phase of acetonitrile, dichloromethane, methanol, and water and a UV detector set at 330 nm. The linearity ranges were 25-250 ng/mL for trans-retinoic acid and vitamin A, and 100-1,000 ng/mL for beta-carotene. This LC method for the determination of retinoids is simple, precise, and accurate. No extraction procedure is required before the chromatographic analysis; only a suitable dilution is necessary. The method proved to be reliable, fast, and economical. Furthermore, this method is indicative of stability, because it allows for the determination of degradation products such as 13-cis-retinoic acid.

Three different analytical methods for the quality control of clozapine in commercial formulations were developed and compared: a liquid chromatographic (LC) method with UV detection, a capillary zone electrophoretic (CZE) method, and a linear scan voltammetric (LSV) method. The isocratic LC procedure used a C18 reversed-phase column; the CZE method used an uncoated fused-silica capillary and phosphate buffer containing polyvinylpyrrolidone as the background electrolyte; the LSV method analyzed clozapine solutions with acidic phosphate buffer as the supporting electrolyte. The 3 methods gave similar and satisfactory results, in terms of precision and accuracy. Repeatability and intermediate precision were good (RSD% < 2.2) and accuracy, resulting from recovery studies, was between 98 and 102%. The rapidity of analysis was high for all 3 methods, especially for the LSV.

In modern practice, the treatment of Parkinson's disease and syndrome is carried out using pharmaceutical formulations containing a combination of levodopa and a decarboxylation inhibitor (carbidopa or benserazide). Two pharmaceutical formulations were quantified by capillary zone electrophoresis using two procedures which differed only in the kind of background electrolyte used. One procedure used a 25 mM phosphate buffer, pH 2.5, while the second one used a 25 mM borate buffer, pH 8.5. The electrophoretic analysis was carried out using an uncoated fused- silica capillary, a separation voltage of 20 kV with currents typically less than 60 microA, and spectrophotometric detection at 205 nm. Calibration curves were performed for levodopa (concentration range 1-100 microg/mL), for carbidopa and benserazide (1-50 microg/mL), and the plots of the peak area versus concentration were found to be linear with a correlation coefficient better than 0.9990. Satisfactory results were obtained when commercial tablets were analyzed in terms of accuracy (98-102%), repeatability (0.6-2.0%), and intermediate precision (1.1-2.6%).

Two antipsychotic drugs (clozapine and loxapine) and six metabolites, N-demethylclozapine, clozapine N-oxide, N-demethylloxapine (amoxapine), 7-hydroxyloxapine, 8-hydroxyloxapine, 8-hydroxyamoxapine, were separated by capillary zone electrophoresis. Variation of pH and ionic strength of the acidic phosphate buffer (pH below 4) did not enable the separation of loxapine and one of its metabolites. Resolution of the single parent drugs and their metabolites was possible in background electrolytes (phosphate, pH 3.5, 60 mmol/l) containing either 0.2% (w/v) polyvinylpyrrolidone as replaceable pseudo-stationary phase, or 0.75 mmol/l beta-cyclodextrin added as complex-forming agent. Full separation of the mixture with baseline resolution of all analytes was obtained with a background electrolyte with heptakis-6-sulfato-beta-cyclodextrin added as negatively charged complexation agent with improved separation selectivity.

Several strategies to improve the separation of 11 central nervous system drugs (antipsychotics and antidepressants) with capillary zone electrophoresis were applied: the variation of the pH of the buffering background electrolyte, its ionic strength, addition of inclusion-complex forming beta-cyclodextrin or polyvinylpyrrolidone (PVP), respectively, as a replaceable, soluble, polymeric pseudo-stationary phase. Best separation was achieved at pH 2.5 and 35 mmol/l ionic strength (phosphate buffer), with 0.5% (w/v) PVP.

Purpose: To evaluate the intraocular penetration of lidocaine 4% topically applied before phacoemulsification., Settings: Institute of Ophthalmology, University of Verona, and Department of Medical Pharmacology, University of Padua, Italy., Methods: Thirty eyes having phacoemulsification for senile cataract were anesthetized by topical application of lidocaine 4%. The drug was applied 3 times in 30 minutes in 15 eyes and 6 times in 60 minutes in 15 eyes. At the beginning of surgery, aqueous humor samples were obtained to measure the lidocaine levels. Blood samples were obtained in 6 patients 30 and 60 minutes after aqueous humor collection. The aqueous humor levels were compared with the amount of pain perceived by patients during surgery., Results: Mean aqueous humor lidocaine concentration was 8.68 micrograms/mL +/- 2.43 (SD) after 3 instillations and 23.21 +/- 8.87 micrograms/mL after 6 instillations. Blood levels of lidocaine were negligible. Patients whose intraocular level was below 12 micrograms/mL perceived more pain during surgery. Only 2 eyes had these low levels after 6 instillations., Conclusions: Topically applied lidocaine 4% effectively penetrates the eye, providing analgesia for phacoemulsification. We suggest at least 6 instillations in the hour preceding surgery. In this study, pain during surgery was primarily related to poor intraocular levels of the anesthetic agent.

Objectives: To verify corneal topography and astigmatism after cataract surgery with 8 mm scleral tunnel incisions closed with a continuous 10-0 nylon suture., Setting: Institute of Ophthalmology, University of Verona, Italy., Method: Twenty eyes were studied for 12 months after cataract extraction with 8 mm, sutured, scleral tunnel incisions. Corneal topography (EyeSys 2.1) was evaluated for the first 5 months. Astigmatism (absolute and induced) was measured by Javal ophthalmometry preoperatively and 1, 7, 30, 60, 90, 150, and 360 days after surgery., Results: In the week following surgery, corneal shape was minimally affected and uncorrected visual acuity was not compromised. Mean with-the-rule induced cylinder was less than 1.00 diopter (D). After 5 and after 12 months, the mean induced cylinder was still less than 1.50 D but with an against-the-rule shift in almost all eyes., Conclusions: Sutured 8 mm tunnel incisions showed good results in terms of absolute cylinders but late against-the-rule shift could not be avoided.

Purpose: To compare the results of secondary implantation of angle-supported anterior chamber intraocular lenses (IOLs) and scleral-fixated posterior chamber lenses., Setting: Eye Clinic, University of Verona, Italy., Methods: This study of 68 eyes of 60 patients comprised two groups. In Group A (n = 35), an angle-supported anterior chamber IOL was implanted and in Group B (n = 33), a scleral-fixated posterior chamber IOL. Follow-up was from 12 to 45 months., Results: In Group A, one eye developed a retinal detachment and another, pseudophakic bullous keratopathy. In Group B, one eye had a major intraoperative choroidal hemorrhage and two developed a retinal detachment postoperatively. All other complications were minor., Conclusions: Although the rate of sight-threatening complications was about 6% for both groups, scleral-fixated posterior chamber IOLs were associated with more intraoperative and postoperative complications than angle-fixated anterior chamber IOLs, and surgery took longer. Thus, anterior chamber IOL implantation should be considered for older patients with relatively good endothelial cell counts.

This prospective study assessed visual results and subjective rehabilitation after cataract surgery in eyes with a preoperative acuity of 0.4 (20/40) or better. Fifty eyes (50 patients) were entered in the study. Corrected and uncorrected visual acuity, lens opacity, glare disability, and contrast sensitivity were measured before surgery and four months after surgery. Patient satisfaction was also measured. Best corrected visual acuity was 0.54 +/- 0.12 before surgery and 0.95 +/- 0.15 four months after surgery. Uncorrected visual acuity was 0.24 +/- 0.18 before and 0.58 +/- 0.27 after surgery. Impairment of corrected visual acuity from glare decreased from 0.12 +/- 0.09 before surgery to 0.04 +/- 0.08 four months after surgery. Contrast sensitivity at 6 cycles/degree increased from 2.71 +/- 0.94 units to 4.73 +/- 1.09 units. After surgery, 62% of patients judged their vision to be greatly improved, 32% judged it improved, 6% judged it unchanged. The patient's satisfaction was partially related to the improvement in uncorrected visual acuity. We conclude that cataract surgery can benefit eyes with limited visual impairment if the surgery is uncomplicated and IOL power is calculated correctly.

Fifteen children aged less than 11 years, affected by congenital glaucoma, underwent visual field testing using two different methods: conventional computerized perimetry (24-2 Humphrey program) and High Pass Resolution perimetry (Ring test). The aim of the study was to discover which of the two perimetric techniques was more suitable for younger patient. Results showed that HPR perimetry is more suitable to children. Reasons include the short duration of the test (5 min), and the appearance like a pleasant game to 80% of the subjects tested. In addition it proved to be better than Humphrey test because of the minimal possibilities of memorisation with a reproducibility factor of 68% in our sample and because of the reliable results and satisfactory evaluation in 76% of the eyes examined.

The therapeutic efficacy of the synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind placebo-controlled study in parallel groups in the management of recurrences in 235 children with recurrent tonsillitis. The ambulant study provided for 15 days of treatment with two oral vials of pidotimod 400 mg or placebo daily, in accordance with a randomisation list, 60 days of treatment with one oral vial of pidotimod 400 mg or placebo daily, and a 90-day follow-up period. The total trial period was 165 days. In addition to evaluating the number of tonsillitis recurrences which occurred during the 75 days of treatment and the 90-day follow-up period, the number of days on which the principal symptoms of the illness were present and on which drugs such as antibiotics or anti-inflammatory agents were used concomitantly, as well as the number of days' absence from school, were analyzed. The findings showed that, taking the treatment phase and the three-month follow-up period together, pidotimod significantly reduces the incidence of inflammatory upper airways episodes. The very low incidence of adverse effects, which was the same as that in the placebo group, confirmed the excellent safety of the product.

We compared three nucleus delivery procedures used during extracapsular cataract extraction (ECCE) after capsulorhexis in 142 eyes. In 25 eyes, the nucleus was expressed through a capsulorhexis 7 mm or wider. In 40 eyes, the nucleus was broken into two pieces and removed through a capsulorhexis 6 mm or less. In 77 eyes, viscoexpression was used to remove the nucleus from the capsular bag through a capsulorhexis 6 mm or less. Nucleus expression after a wide capsulorhexis was successful in 68% of the eyes in which it was attempted. Nucleus fragmentation was successful in 90%. Postoperative inflammation was high in both of these groups. Nucleus viscoexpression was successful in 93%, with low postoperative inflammation. Although it requires a 7- to 8-millimeter corneoscleral incision, based on our study, viscoexpression would appear to be the best nuclear delivery technique when ECCE, rather than phacoemulsification, is being performed.

A study was carried out on 110 patients with various diseases related to chronic inflammation of the tonsils and to hypertrophic adenoids. Sixty-two of these patients underwent adenotonsillectomy, while the others were followed clinically and, where necessary, given medical treatment. At the first observation the patients were between the ages of 2 and 12 (mean age 6.1 years). At the start of the present study the patients ages ranged from 10 to 22 (mean age 17 years). Clinical follow-up was carried out on the patients 2 and 7 years after the first observation and/or adenotonsillectomy. The patients were divided into homogeneous groups according to the severity of symptoms. The A.A. evaluated changes of the following clinical parameters: annual frequency of inflammatory pharyngotonsillar episodes, nasal respiratory obstruction, sore throat, otologic pathology. Evaluations were carried out statistically in each group. After more than 7 years from surgery, the significant reduction of various diseases related to chronic inflammation of the tonsils and to hypertrophic adenoids, in accordance with the findings after 2 years from surgery, underline the effectiveness of adenotonsillectomy in correctly selected candidates.

This report evaluates the validity of a preventive programme in a population which underwent refractometric screening at the ages of 20 months and 4 years. In 1987, 1,046 children born in 1985 in the territory of the Veneto National Health Unit No. 19 were invited to undergo screening for amblyogenic factors such as meridional hyperopia greater than or equal to +2.50 diopters (D), myopia less than or equal to -2.50 D, anisometropia greater than or equal to 2 D, opacity of the dioptric media and strabismus. The test method was non-cycloplegic photorefractometry (PhR). Seven hundred and ninety-five children were tested (76%); positive cases underwent subsequent cycloplegic autorefractometry (AR) and corrective lenses were prescribed as necessary. In 1989, an eye test was performed on 653 children who had taken part in the previous PhR screening and on 350 similar children who had not: the test included evaluation of visual acuity, stereopsis and AR. An eye with a corrected visual acuity of less than 0.7 was considered amblyopic. PhR demonstrated a sensitivity of 80%, a specificity of 96% and a positive prediction rating of 46% in the identification of amblyogenic factors. The prevalence of amblyopia at 4 years of age in the group which had undergone previous screening was 1.07% vs. 2.57% in the group which had not (P: not significant). The progress of the myopia was studied in a group with full optical correction used continuously (Group A) and in a control group under-corrected by at least 1.5 D (Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

The CO2 Laser is used in the treatment of several laryngeal diseases and offers considerable advantages over traditional techniques. New applications of this surgical tool are currently under study for other laryngeal and ENT pathologies. It should be pointed out that there are some limitations to the use of the CO2 Laser; an accurate examination of its indications is needed, as well as a precise knowledge of its techniques and possibilities.