Study of antifungal agent caspofungin adsorption to laboratory materials.

Treatment of invasive fungal infections with Caspofungin is used as the first-line antifungal agents. The minimum inhibitory concentration value is a test which indicates the degree of sensitivity of a strain regarding a drug. However, no value of minimum inhibitory concentration for caspofungin is available because very variable value is obtained. In this work, we study the link with the adsorption phenomenon of CSF previously described in literature and the lack of minimum inhibitory concentration value. A systematic study of the impact of different parameters on CSF adsorption is reported. The effect of the nature of container material, the aqueous solution pH and the organic solvent proportion was studied. In addition, the possibility of using a coating agent to minimize the adsorption was assayed and evaluated. Results obtained showed the importance of the material used during the manipulation of CSF. The use of acidic pH aqueous solution or the addition of acetonitrile or methanol proportions (50 % and 70 %, respectively) were found efficient to avoid adsorption of CSF on glassware material, which is the relevant strategy for analytical samples of caspofungin. The treatment of HPLC glass vials and 96-well plates with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane reduced the adsorption. The significant adsorption observed in this work especially with plastic materials, questions the results obtained before in different assays and explained the absence of MIC value.

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Estimation of the post-mortem interval of human skeletal remains using Raman spectroscopy and chemometrics.

An important demand exists in the field of forensic analysis to objectively determine the post-mortem interval (PMI) when human skeletal remains are discovered. It is widely known that bones undergo different chemical and physical processes after death, mainly due to their interaction with the environment in which they are found, although it is not known exactly what these processes consist of. Multiple techniques have been used so far to follow up these and other post-mortem changes and thus establish the time elapsed since the individual's death, but they present important drawbacks in terms of reliability and accuracy. The aim of this research was to propose an analytical methodology capable of determining the PMI by using non-destructive Raman spectroscopy measurements of human skeletal remains. The recorded Raman spectra provided valuable and potentially useful information from which a multivariate study was performed by means of orthogonal partial least squares regression (OPLSR) in order to correlate the PMI with the detected spectral modifications. A collection of 53 real human skeletal remains with known PMI (15 years ≤ PMI ≤ 87 years) was analysed and used for building and validating the OPLS model. The PMI of 10 out of 14 validation samples could be determined with an accuracy error of less than 30%, demonstrating the adequate predictive performance of the OPLS model even in spite of the large inter-individual variability it handled. This opens up the possibility of applying the OPLS model in combination with non-destructive techniques to the determination of the PMI of human skeletal remains that have been buried in conditions similar or equal to those of cemetery niches and in a geographic location with a Mediterranean climate, which is an important achievement for forensic medicine and anthropology.

Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD.

The actual scenario in the fight against fungal infections forces researchers to carry through with resistance studies to improve the therapies. These studies, which are performed in cell culture media, need accurate and sensitive analytical methodologies. That is why, in this work, an analytical method for caspofungin (CSF) concentration determination in RPMI-1640 cell culture medium with on-line sample treatment was developed and validated. CSF concentration was determined by HPLC-FLD using a column-switching procedure. The chromatographic analysis was carried out in less than 10 min using a C8 column (4 × 4 mm, 5 µm) as extraction stationary phase and a HSS T3 column (4.6 × 100 mm, 5 µm) as the analytical column. The used mobile phases were mixtures of phase A: pH 2 (adjusted with TFA) aqueous phase and phase B: ACN. For the extraction, the composition was (95:5, A:B v/v) and for the analysis (60:40, A:B v/v), both done in isocratic elution mode. These chromatographic conditions allowed reaching a limit of quantification of 10 µg/L, using 100 µL of sample with an injected volume of 40 µL. The proposed method was successfully validated in terms of selectivity, carryover, linear concentration range, accuracy and precision according to the criteria established by the Food and Drug Administration. Available amount of CSF in RPMI-1640 solution was found critical. CSF concentrations remained stable up to 2 h at room temperature. The developed method was applied for the direct analysis of CSF concentrations from in vitro experiments in presence of C. glabrata (CAGL18). The results highlight the decrease of cell proliferation even if the CSF amount decreases too, which asks question about the real value of the efficient concentration for CSF antifungal activity.

Micellar electrokinetic chromatography method for the determination of several natural red dyestuff and lake pigments used in art work.

The identification of organic colorants used in artistic paintings is an important information source for reconstructing the working techniques found in a particular work and for defining a programme for the restoration and conservation of the painting. In this work, sodium dodecyl sulfate (SDS) was used as a surfactant in micellar electrokinetic chromatography (MEKC) for separating a broad range of red organic pigments, based on their colouring matters: madder (colouring matters: alizarin, quinizarin and purpurin), cochineal (colouring matter: carminic acid), red sandalwood (colouring matter: santalin), brazilwood (colouring matter: brazilin), lac dye (colouring matter: laccaic acid) and dragon's blood (colouring matter: dracorhodin). The running electrolyte used was 20 mM borax (pH 9), containing 20 mM SDS and 10% acetonitrile as organic modifier. Separation was carried out by applying a +20 kV voltage at the injection end, 25 degrees C and 214 nm/254 nm as detection wavelengths. All colorants were separated within less than 13 min with a good baseline resolution. The method was applied to the analysis of paint samples obtained from the Diocesan Museum of Holy Art of Bilbao.

Graphene oxide electrodeposited electrode enhances start-up and selective enrichment of exoelectrogens in bioelectrochemical systems.

This study seeks to assess the impact that the anodic electrodeposition of graphene oxide (GO) has on the start-up process and on the development of microbial communities on the anode of BESs. The GO electrodeposited electrodes were characterised in abiotic conditions to verify the extent of the modification and were then transferred to a bioelectrochemical reactor. Results showed that the modified electrode allowed for a reduced start-up time compared to the control electrode. After three months, high throughput sequencing was performed, revealing that electrochemically reduced graphene oxide acts as a selective agent toward exoelectrogenic bacteria as Geobacter. Overall, this study shows that GO modified electrodes enhance biofilm build up in BES.

Quantitative determination of dobutamine in newborn pig plasma samples by HPLC-MS/MS.

A novel gradient reverse phase high performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) was performed as a method for the determination of dobutamine hydrochloride (DOB) in newborn pig plasma samples. It was developed and validated after optimization of sample treatment and various chromatographic and mass spectrometric conditions. Trimethoxydobutamine (TMD) was used as internal standard. Heptafluorobutyric acid (HFBA) and ethyl acetate were used for the treatment of plasma samples. The separation of dobutamine and internal standard was done using a Kinetex F5 (50×2.1mm, 2.6µm, 100Å) analytical column. The mobile phase was a mixture of acetonitrile and HCOOH 0.01%. The column oven temperature was optimized at 40° C and the flow rate was 0.25mL/min. DOB and TMD were detected by multiple reaction monitoring (MRM) mode in ESI+, using a cone voltage (CV) of 25V and a collision energy (CE) of 25eV. The weighted calibration curve (1/x2) was found to be linear over the concentration range of 1-100ng/mL (r2>0.999). The limit of quantification (LLOQ) of the method was 1ng/mL. The values of selectivity, carryover, LLOQ, linearity, accuracy, precision, matrix effect, stability and recovery obtained meet the acceptable range according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines. The method was efficiently applied to quantify DOB in plasma samples from a pharmacokinetic/pharmacodynamic study in a disease model of newborn piglet.

Validation of a solid phase extraction-high performance liquid chromatographic method for the determination of eprosartan in human plasma.

In this work, a solid phase extraction-reversed phase high performance liquid chromatographic (SPE-RP-HPLC) method with photometric detection for monitoring the antihypertensive drug eprosartan has been validated in order to assure good quantitation of eprosartan in plasma samples obtained from patients under cardiovascular treatment. This analytical method was developed by using experimental design and quantitation was accomplished with the internal standard method. No interferences were observed from endogenous compounds of plasma and other drugs which are commonly co-administered in elderly patients. The recoveries of eprosartan from plasma samples, measured at three levels of the linear concentration range (150-4000 ng/mL) were found to be between 93.4 and 102.8%. The intraday and interday precision and accuracy (measured by relative standard deviation, RSD, and relative error, RE, respectively) were always lower than 13% (RSD) and 4% (RE). Stability studies showed that eprosartan stock solutions are stable for at least 3 months when stored at 8 degrees C and plasma samples containing the drug were stable at least during the whole analytical method.

Effect of coating on the environmental applications of zero valent iron nanoparticles: the lindane case.

Commercial stabilized slurry of zero-valent iron nanoparticles (nZVI) as well as laboratory-synthesized polymer-stabilized NZVI nanoparticles were used for lindane (γ-hexachlorocyclohexane) degradation studies in aqueous solution. In the present study, polymer-stabilized iron nanoparticles were stabilized using polyethylene glycol (PEG, Mn ~400 and ~950-1050) and polytetrahydrofuran (PTHF, Mn ~650). To study the effectiveness of the different nanoparticles, a quantitative monitorization of lindane degradation by using solid-phase extraction (SPE) and a qualitative measurement of generated volatile by-products by headspace-solid phase microextraction (HS-SPME) followed by GC/MS were carried out. The obtained data were compared and contrasted with the results obtained in previous work. Results showed that the nanoparticles studied in this work possess superior dechlorination performance compared with previous observations. The freshly prepared Fe(0)-PEG400, Fe(0)-PEG1050 and Fe(0)-PTHF exhibited high reactivity during the dechlorination process of lindane in a very short time. The results obtained with the synthesized nanoparticles were similar to those obtained with commercial nanoparticles. However, in all cases reactivity decreased at reaction's late stage. Degradation of lindane by the studied nanoparticles removed 99.9% of the lindane initial concentration after 72h, except for Fe(0)-PTHF nanoparticles, for which the reaction stopped after 5min. In all cases, the reaction followed a second order kinetics. Finally, comparing the results from this study with our previous work, where different nature polymers were considered (Fe(0)-CMC, Fe(0)-PAA and Fe(0)-PAP), more gradual degradation profile of lindane was observed for Fe(0)-PAA and Fe(0)-CMC. It should be noted that in the present case, the reaction of lindane was speeded up with commercial and Fe(0)-PEG nanoparticles. Nevertheless, in the later case, the composition of by-products was affected by the presence of partially degraded intermediates. Taking into account the current technologies, the high removal rates obtained and the acceptable degradation times required, the proposed technology is suitable for its aimed purpose.

DATINK pilot study: an effective methodology for ballpoint pen ink dating in questioned documents.

Establishing the approximate age of an ink entry from a questioned document is often a complicated task and a controversial issue in forensic sciences. Among the existing approaches, the analysis of solvents in ballpoint inks may be a useful parameter for determining the age of ink on paper. In recent years, several ink dating methods have been proposed. These methods have been based on the analysis of common ink solvents using gas chromatography/mass spectrometry (GC/MS) as the analytical platform. Despite these recent methods, several questions remain. The aim of this work was to develop an ink dating methodology (DATINK) for documents written by ballpoint pens based on the disappearance of volatile solvents from the ink entry. Multiple solid-phase microextraction (MHS-SPME) coupled to GC/MS was used to measure the solvents from ink entries made with four BIC(®) ballpoint pens. The ß parameter, the remaining fraction of the analyte in the system after one equilibration, corresponding to the successive extractions was considered for modelling a mathematical equation for later ink age dating. Preliminary tests of DATINK method showed that it was possible to detect the presence of ink solvents on documents up to the studied five years. The analyses of different real samples of known age were analyzed in terms of ß values, which provided a mean relative error of 21%. The proposed use of ß parameter for estimating the absolute age of ballpoint ink entries has shown promising results with a standard deviation of ß ranging from 0.002 to 0.004.

Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS.

In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 µL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h).

Comparison between the effects of VIP and the novel peptide PACAP on the exocrine pancreatic secretion of the rat.

The effect of intravenous infusion of pituitary adenylate cyclase-activating peptide (PACAP) 27, a novel regulatory peptide that shows a close structural and chemical similarity to vasoactive intestinal peptide (VIP), on the rat exocrine pancreatic secretion was studied. PACAP and VIP stimulated the flow rate of exocrine pancreatic secretion (p < 0.05). However, protein output and amylase secretion were mainly stimulated by PACAP. Intravenous infusion of VIP increased the plasma levels of secretin (p < 0.05). On the other hand, PACAP released neither secretin nor VIP. Our results show: (a) both PACAP and VIP stimulate exocrine pancreatic secretion, (b) PACAP stimulation of pancreatic amylase and protein secretion is greater than that induced by VIP, and (c) PACAP probably exerts a direct effect on exocrine pancreas whereas some of the actions of VIP might be mediated by secretin.

Determination of aldicarb, aldicarb sulfoxide and aldicarb sulfone in some fruits and vegetables using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

An analytical method for the determination of aldicarb, and its two major metabolites, aldicarb sulfoxide and aldicarb sulfone in fruits and vegetables is described. Briefly the method consisted of the use of a methanolic extraction, liquid-liquid extraction followed by solid-phase extraction clean-up. Afterwards, the final extract is analyzed by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). The specific fragment ion corresponding to [M-74]+ and the protonated molecular [M+H]+ ion were used for the unequivocal determination of aldicarb and its two major metabolites. The analytical performance of the proposed method and the results achieved were compared with those obtained using the common analytical method involving LC with post-column fluorescence detection (FL). The limits of detection varied between 0.2 and 1.3 ng but under LC-FL were slightly lower than when using LC-APCI-MS. However both methods permitted one to achieve the desired sensitivity for analyzing aldicarb and its metabolites in vegetables. The method developed in this work was applied to the trace determination of aldicarb and its metabolites in crop and orange extracts.

Fast screening method for the determination of angiotensin II receptor antagonists in human plasma by high-performance liquid chromatography with fluorimetric detection.

A selective, accurate and precise high-performance liquid chromatographic assay coupled to fluorescence detection was developed for the detection of some angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan, Candesartan cilexetil and its metabolite Candesartan MI. The analytes and the internal standard (bumetanide, a high-ceiling diuretic) were extracted from plasma under acidic conditions by means of solid-phase extraction using C8 cartridges. This procedure allowed recoveries close to 80% for all these drugs excluding Candesartan cilexetil (70%) which presented adsorption processes on glass and plastic walls. The analytes and potential interferences were separated on a reversed-phase column, muBondapak C18, at room temperature. A gradient elution mode was used to carry out the separation, the optimal mobile phase being composed of acetonitrile-5 mM acetate buffer, pH 4, at variable flow-rates (from 1.0 to 1.2 ml/min). Fluorescence detector was set at an excitation wavelength of 250 nm and an emission wavelength of 375 nm. Intra- and inter-day relative standard deviations for all the compounds were lower than 8% except for Losartan (12%) and the method assesses a quite good accuracy (percentage of relative error approximately 6% in most of the cases). The limit of quantitation for these compounds was 3 ng/ml for Candesartan cilexetil and M1, 16 ng/ml for Losartan and 50 ng/ml for Irbesartan and Valsartan, which allows their determination at expected plasma concentration levels. This assay method has been successfully applied to plasma samples obtained from hypertensive patients under clinical studies after oral administration of a therapeutic dose of some of these ARA II compounds.

Quantitative determination of oxprenolol and timolol in urine by capillary zone electrophoresis.

A simple capillary zone electrophoretic method with UV detection has been developed for the quantitative determination of the beta-adrenoreceptor antagonists (beta-blockers) oxprenolol and timolol in human urine, preceded by a solid-phase extraction step. The electrophoretic separation was performed on a 78 cm x 75 microm I.D. fused-silica capillary (effective capillary length: 70 cm). The electrolyte consisted of a Na2B4O7-H3BO3 (50 mM), pH 9. The introduction of the sample was made hydrostatically for 20 s and the running voltage 25 kV at the injector end of the capillary. Photometric detection was used at a wavelength of 229 nm for oxprenolol and 280 nm for timolol. Under these conditions oxprenolol migrated at 4.76+/-0.05 min and timolol at 4.97+/-0.05 min. The solid-phase extraction methods were optimised for each beta-blocker and provided recoveries of 72.8% for timolol and 94.52% for oxprenolol. Good resolution from the endogenous compounds present in the urine matrix were achieved for both compounds. The method was applied to the determination of both beta-blockers in pharmaceutical formulations and urine samples obtained from hypertensive patients after the ingestion of a therapeutic dose (in a 24-h time interval after the ingestion). The quantitative results were compared with results previously obtained at our laboratories by HPLC and were found to be in good agreement. Good reproducibility, linearity, accuracy and quantitation limits (in urine) of 0.19 microg/ml for timolol and 0.20 microg/ml for oxprenolol were obtained, allowing the method to be applied to pharmacokinetic studies of these compounds.

High-performance liquid chromatography with amperometric detection applied to the screening of 1,4-dihydropyridines in human plasma.

A high-performance liquid chromatographic method with electrochemical detection has been developed for the determination of six 1,4-dihydropyridines: nifedipine, nimodipine, nisoldipine, nicardipine, felodipine and lacidipine. The chromatographic separation was performed using a Supelcosil LC-ABZ+Plus C18 column. A mobile phase of methanol-water (70:30), containing 2 mM CH3COOH-CH3COONa at a flow-rate of 1 ml/min and a pH of 5.0, was used. The temperature was optimized at 30+/-0.2 degrees C. The amperometric detector, equipped with a glassy carbon electrode, was operated at 1000 mV versus Ag/AgCl in the direct current mode. The method was applied to the determination of these compounds at ng/ml concentrations, obtaining intra-day reproducibilities of lower than 5.0% in terms of relative standard deviations and detection limits ranging from 16 to 44 ng/ml. The method was applied to the screening of 1,4-dihydropyridines in spiked plasma samples, with a total elution time of lower than 18 min, obtaining the best recoveries for nimodipine and felodipine (91 and 88%, respectively). These recoveries together with the low detection limits achieved allow its application to the analysis of these drugs in human plasma.

Micellar electrokinetic chromatography as a fast screening method for the determination of 1,4-dihydropyridine calcium antagonists.

A micellar electrokinetic chromatographic method (MEKC) was optimized for the separation of six calcium antagonists. The effects of the buffer (concentration and pH), concentration of sodium dodecyl sulphate (SDS), the organic modifier, the injection time, and the voltage applied were studied. A final appropriate electrolyte of 50 mM borate buffer, pH 8.2, containing 20 mM SDS and 15% (v/v) acetonitrile was found to provide the optimum separation with respect to resolution and migration time. The samples were introduced hydrostatically for 4 s at 50 mbar injection pressure and the applied voltage was +25 kV. The screening of the six compounds was achieved in less than 15 min: nifedipine (migration time, tm = 6.9 min), nimodipine (tm = 10.1 min), felodipine (tm = 12.2 min), nicardipine hydrochloride (tm = 12.7 min), lacidipine (tm = 13.5 min) and amlodipine besylate (tm = 14.1 min, tm = 8 min). The method developed showed to be linear at least up to 70 micrograms/ml with a detection limit of about 5 micrograms/ml for each compound. The within-day and inter-day area reproducibility (R.S.D.) were, respectively, lower than 4.8 and 8.6% for six replicate samples.

Capillary zone electrophoresis applied to the determination of the angiotensin-converting enzyme inhibitor cilazapril and its active metabolite in pharmaceuticals and urine.

A capillary zone electrophoresis method has been developed for the quantitation of antihypertensive drug cilazapril and its active metabolite cilazaprilat in pharmaceuticals and urine. The separation of the compounds was performed in a fused-silica capillary filled with the running electrolyte, which consisted of a 60 mM borate buffer solution at pH 9.5. Under the optimized experimental conditions, the separation took less than 5 min. The analysis of urine samples required a previous solid-phase extraction step using C8 cartridges. The method was successfully applied to the determination of the drug and its metabolite in urine samples obtained from three hypertensive patients (detection limits of 115 ng ml(-1) for cilazaprilat and 125 ng ml(-1) for cilazapril) and to pharmaceutical dosage forms. The method was validated in terms of reproducibility, linearity and accuracy.

Capillary electrophoresis as a useful tool for the analysis of chemical tracers applied to hydrological systems.

A capillary electrophoretic method was optimised for the separation and determination of iodide used as artificial tracer in hydrology. The influence of the buffer concentration and pH, electroosmotic flow modifier concentration (cetyltrimethylammonium bromide (CTAB)), the injection time and voltage applied, on the electrophoretic separation was studied. A running buffer of 20 mM phosphate (pH 8) containing 1 mM CTAB was found to provide the optimum separation of iodide with respect to resolution, migration time and selectivity. The water samples were injected hydrostatically at 10 cm for 110 s, the voltage applied was -20 kV and a detection wavelength of 214 nm. The influence of the sulphite added to water samples in order to prevent the oxidation of iodide to iodate was also studied. This method can be applied to the determination of iodide free of sulphite interference up to at least a ratio of 1:1000 (I(-):SO3(2-)). The other inorganic anions, which are present in the water samples (mainly chloride, sulphate, nitrate, carbonate), do not interfere with the determination of iodide. This method allows the simultaneous determination of bromide, nitrite, and nitrate together with iodide. The electrophoretic method showed to be linear from 0.5 to 5 mg l(-1) of iodide (the migration time was 2.6 min) with a quantitation limit of 0.45 mg l(-1) and a intraday repeatability lower than 4% of R.S.D. at different concentration levels.

Determination of the beta-blocker atenolol in plasma by capillary zone electrophoresis.

A capillary zone electrophoretic method was optimised for the determination of the beta-blocker atenolol in plasma. Separation was performed in an uncoated silica capillary of 58.5 cm (effective length 50 cm) x 75 microm I.D., and detection was at 194 nm. The effects of the buffer (concentration and pH), the injection time, the voltage applied and the plasma clean-up procedure were studied. The determination of atenolol was achieved in less than 3 min, using an electrolyte of 50 mM H3BO3-50 mM Na2B4O7 (50:50, v/v) pH 9, injected hydrodynamically for 4 s at 50 mbar and applying a voltage of +25 kV. This method was applied to the determination of atenolol in plasma of nine hypertensive patients (male and female, aged from 39 to 73 years). Atenolol concentrations found vary from 30 to 585 ng/ml.