Selective potentiometric determination of zolpidem hemitartrate in tablets and biological fluids by using polymeric membrane electrodes

The construction and electrochemical response characteristics of 4 polymeric membrane sensors were investigated for potentiometric determination of zolpidem hemitartrate. The construction of the 4 sensors was based on the formation of ion-pair complexes between the drug cation and ionic sites in the ratio of 1:2, respectively. Two of the sensors were constructed by using ammonium reineckate or ammonium tungstate as the fixed ionic site in a polymeric matrix of polyvinyl chloride (PVC) (sensors 1 and 2). Linear responses over the concentration range of 10(-5)-10(-3)M, with cationic slopes of 30 and 30.7 mV per concentration decade, were obtained by using sensors 1 and 2, respectively. The third sensor was fabricated by using PVC carboxylate (PVC-COOH). The dissociated COOH groups in the PVC-COOH act as a mediator and/or ionic site. A linear response was obtained over the concentration range of 10(-5)-10(-2)M with a cationic slope of 29 mV per concentration decade. Sensor 4 was fabricated by using 2,6-didodecyl-beta-cyclodextrin as the ionophore, polyurethane (Tecoflex) as a polymeric matrix, and potassium tetraphenyl borate as the ionic site; it showed a linear response over the concentration range of 10(-7)-10(-2)M with a cationic slope of 28.9 mV per concentration decade. The direct potentiometric determination of zolpidem hemitartrate in pure forms by using the 4 proposed sensors gave average recoveries of 98.5+/-0.7, 99.4 +/-0.2, 100.7+/-0.10, and 99.8+/-0.1% for sensors 1-4, respectively. The results obtained by the proposed procedures were statistically analyzed and compared with those obtained by using a reported method. The 4 proposed sensors were also applied successfully to the determination of the drug in tablets and in biological fluids. Average recoveries obtained by using sensors 1, 2, 3, and 4 for drug assay of tablets were 99.6+/-0.6, 100+/-0.7, 99.7+/-0.4, and 99.5+/-0.8%, respectively. The presence of tablet excipients did not interfere with the determination of the drug or with the accuracy and precision of the 4 proposed methods. The methods were also used to determine the drug in the presence of its degradates and thus could be used as stability-indicating methods.     

Amperometric determination of acetylsalicylic acid in drugs by batch injection analysis at a copper electrode in alkaline solutions

This paper describes the determination of acetylsalicylic acid (ASA) as salicylate (SA) in pharmaceutical formulations by using amperometric detection with copper electrodes in 0.10 mol l(-1) NaOH solution. Batch injection analysis (BIA) was explored for this application. The system exhibited sharp current response peaks, rapid washout and excellent repeatability. A large linear dynamic range from 1 to 1000 mumol l(-1) was obtained by using an injected volume of 100 mul, with a detection limit of 0.48 mumol l(-1). R.S.D. of 0.37% for 30 repetitive (1x10(-4) mol l(-1)) injections and sampling frequency of 60 h(-1) were achieved. The results obtained using this system for ASA determination in seven different drug samples compared well with those found by spectrophotometry (Trinder test).     

Sodium alginate/HPMC/liquid paraffin emulsified (o/w) gel beads,by factorial design approach; and in vitro analysis

The present study involved development of a novel sodium alginate (SA)/HPMC/light liquid paraffin emulsified (o/w) gel beads containing Diclofenac sodium (DS) as an active pharmaceutical ingredient and its site specific delivery by using hard gelatin capsule fabricated by enteric coated Eudragit L-100 polymer. Emulsified gel beads were formulated by 3-level factorial design, ionic gelatin method. The obtained beads were characterized by Fourier transform infrared, X-ray diffraction and Field emission scanning electron microscope analysis. The variables such as SA (X₁), HPMC (X₂), were optimized for drug loading and in vitro drug release with the help of response surface methodology (RSM). The RSM analysis predicted that SA was significant for both drug loading (p = 0.0005) and drug release (p = 0.0041). HPMC was only significant for drug release (p = 0.0154). The cross-product contribution (2FI) and quadratic model were found to be adequate and statistically accurate with correlation value (R²) of 0.9054 and 0.9450 to predict the drug loading and drug release respectively. An increase in concentration of HPMC and SA decreases the drug loading as well as the drug release. The obtained optimum values of drug loading and DS released were 7.43 % and 85.54 % respectively, which were well in agreement with the predicted value by RSM.     

In situ gelling hexagonal phases for sustained release of an anti-addiction drug

In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 μg/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release.     

High-performance liquid chromatographic analysis of doxacurium, a new long-acting neuromuscular blocker

A rapid and sensitive high-performance liquid chromatographic procedure was developed for the analysis of the new, long-acting neuromuscular blocker doxacurium in the plasma and urine of dog and man and in the bile of dog. Samples were prepared on solid-phase extraction cartridges containing a methyl (C1) bonded phase and were chromatographed on a 15 cm reversed-phase column (C1) using a mobile phase of 0.05 M monobasic potassium phosphate-acetonitrile (30:70, v/v). The compound was detected at 210 nm with a lower limit of quantitation of 10 ng/ml. An inter-assay accuracy of 90-92% was obtained for the analysis of the drug from biological fluids. The method was applied to studies of doxacurium after intravenous administration to dog and man.     

Sensitive high-performance liquid chromatographic assay using 9-fluorenylmethylchloroformate for monitoring controlled-release lidocaine in plasma

A sensitive high-performance liquid chromatographic (HPLC) assay using fluorescence detection for quantifying lidocaine levels in plasma (in the ng/ml range) was developed. This novel HPLC assay has made possible the simultaneous monitoring of lidocaine levels in coronary and peripheral plasma obtained after myocardial controlled-release matrix administration (0.92 mg/kg during 4 h) in the arrhythmic dog. The method employed extracts the drug from plasma using 1-chlorobutane and a subsequent derivatization with 9-fluorenylmethylchloroformate in acetonitrile at 110 degrees C. The derivative was chromatographed on a C18 reversed-phase column and measured with fluorescence detection (excitation 254 nm, emission 313 nm). N-Methylephedrine was found to be suitable as an internal standard, post-derivatization. The derivatization product of lidocaine was identified and characterized by mass spectral analysis. It was found to have a unique and reproducible dicarbamate structure, which was stable for at least three days at room temperature. The method was tested with human plasma as well as on dog plasma. Analytical recoveries were 88.6 +/- 3.6 and 77.4 +/- 3.0% (mean +/- S.E.), respectively, at levels ranging from 25 to 200 ng/ml. The lower detection limit was 1 ng/ml lidocaine. In conclusion, this rapid and convenient analysis was found to be suitable for the bioavailability pharmacokinetic assessment of lidocaine following low-dose regional drug administration.     

Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography

This paper reports the development of a rapid method for the enantioselective analysis of the nonsteroidal anti-inflammatory drug ibuprofen in human plasma by capillary electrophoresis employing the anionic cyclodextrin-modified electrokinetic chromatography mode. Sample cleanup was carried out by acidification with HCl followed by liquid-liquid extraction with hexane:isopropanol (99:1 v/v). The complete enantioselective analysis was performed within 10 min, using 100 mmol L(-1) phosphoric acid/triethanolamine buffer, pH 2.6, containing 2.0% w/v sulfated beta-cyclodextrin as chiral selector; fenoprofen, another nonsteroidal anti-inflammatory drug, was used as internal standard. The calibration curves were linear over the concentration range of 0.25-125.0 microg mL(-1) for each enantiomer of ibuprofen. The mean recoveries for ibuprofen enantiomers were up to 85%. The enantiomers studied could be quantified at three different concentrations (0.5, 5.0 and 50.0 microg mL(-1)) with a coefficient of variation and relative error not higher than 15%. The quantitation limit was 0.2 microg mL(-1) for (+)-(S)- and (-)-(R)-ibuprofen using 1 mL of human plasma. The plasma endogenous compounds and other drugs did not interfere with the present assay. The analysis of real plasma samples obtained from a healthy volunteer after administration of 600 mg of racemic ibuprofen showed a maximum plasma level of 29.6 and 39.9 microg mL(-1) of (-)-(R)- and (+)-(S)-ibuprofen, respectively, and the area under plasma concentration-time curve AUC(0-infinity) (+)-(S)/AUC(0-infinity) (-)-(R) ratio was 1.87.     

Aripiprazole Loaded Polymeric Biodegradable Microspheres: Formulation and In Vitro Characterization

In the present study, we attempted to prepare biodegradable microspheres of polylactic acid containing aripiprazole in order to achieve its controlled release profile suitable for parenteral administration. Biodegradable microspheres were prepared by solvent evaporation method using methylene dichloride as a solvent. The optimization of various formulation variables (e.g., stirring speed, and polymer:drug ratio, stabilizer concentration) to obtain spherical particles was also investigated. The optimized product was further characterized for various in vitro attributes, such as particle size and its distribution, encapsulation efficiency, surface properties, percentage yield, and in vitro release. Changing the ratio of polymer, stabilizers, and leaching agent (sodium chloride) affected the entrapment efficiency and release rate of aripiprazole. The release quantum was 88.41% when stirring rate was 2000 rpm and it was further increased to 94.65% when stirring speed was increased to 3000 rpm (Formulation E). Drug entrapment of microspheres was increased by increasing the concentration of PVP and maximum entrapment (62.35%) was obtained at 4% concentration of PVP (Formulation E). Spherical particles with good surface characteristics were obtained at stirring rate 3000 rpm and drug:polymer ratio 1:10.     

Analysis of the metabolites of ethyl loflazepate by gas chromatography with electron-capture detection

A gas chromatographic assay with electron-capture detection (GC--EC) is described for the metabolites of ethyl loflazepate (Victan), a new benzodiazepine with a potent anti-anxiety activity, in biological fluids. Since the parent drug undergoes a first-pass effect, pharmacokinetic data may only be obtained by measuring the total levels of two of the major metabolites. Accurate data can not be obtained for the metabolites separately since one of them (M1) is chemically transformed to the other (M2) during plasma sampling, storage and extraction. A sensitive, specific and accurate GC--EC assay is developed using a synthetic analogue of M2 as an internal standard. The limit of detection in plasma is approximately 2 ng/ml and the precision about 3% (within-run and between-run). The method is applied to plasma samples collected after oral administration of 2 mg and 4 mg of the drug in tablet form to human volunteers. The results obtained are correlated with those from an existing gas chromatographic--mass spectrometric assay. A very good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques.     

Determination of cefadroxil by sequential injection with spectrophotometric detector.

A sequential injection analysis (SIA) spectrophotometric procedure for cefadroxil determination has been developed. The SIA instrumentation was modified to achieve the desired function and operations by using the software developed to interface the PC with the conventional SIA system. The method is based on the measurement of a red, water-soluble product formed by the reaction between cefadroxil and 4-aminoantipyrine in the presence of alkaline potassium hexacyanoferrate(III) at 510 nm. Optimum conditions for determining the drug were investigated. Beer's law was obeyed over the concentration ranges of 1 - 10 mg L(-1) and 10 - 50 mg L(-1) with a detection limit (3 sigma) of 0.17 mg L(-1) and a limit of quantification (10 sigma) of 0.56 mg L(-1). The relative standard deviations of 1.98% and 1.93% for 5 mg L(-1) and 30 mg L(-1) of the drug, respectively (n = 11) are obtained. The proposed method has been applied satisfactorily to the determination of cefadroxil in commercial pharmaceutical formulations with a sampling rate of 100 h(-1). Results obtained were in good agreement with those obtained by the official HPLC method at the 95% confidence level.     

Electrochemical determination of some antidiabetic drugs for type 2 diabetic patients

Quantitative determination of rosiglitazone, pioglitazone, glimepiride and glyburide as antidiabetic drugs for type 2 diabetic patients was performed conveniently and economically using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Carbon paste (CPE) and glassy carbon (GCE) electrodes were successfully used as sensors for these drugs in Briton-Robinson (B-R) as buffer solution. The preparation of CPE and the GCE as ion selective electrodes is based on the construction of 10% standard drug ion pair with reineckate or tungstophosphate imbedded as electroactive material. Working standards were freshly prepared just before the assay by dilution from a 10⁻² mol L⁻¹ drug stock solution. At a scan rate of 100 mV s⁻¹ the cyclic voltammograms showed a well defined anodic peak with high selectivity. The DVP gave a reproducible well defined diffusion controlled peak for each drug at a scan rate of 10 mV s⁻¹. The oxidation peaks were used to determine the tested drug concentrations. The quantitative determination of the four drugs in their pharmaceutical preparations by the proposed electrochemical technique was found to be identical with the values obtained by the standard HPLC method. A mean % recovery of 100 ± 1 was obtained and the % relative standard deviation was 1.62 indicating the high precision of the method and the confidence in its repeatability. The proposed electroanalytical technique using either the CPE or the GCE is economic, selective and can be applied for both the qualitative and quantitative determination of the drugs in their pharmaceutical preparations, without special drug separation.     

Capillary electrophoresis method for the determination of isradipine enantiomers: stability studies and pharmaceutical formulation analysis

A simple enantioselective method based on CE using CD as chiral selector was developed and validated for the determination of isradipine (IRD) enantiomers in a pharmaceutical formulation and for the determination of IRD enantiomers in degradation studies. After optimization, the best results were obtained using 15 mM borate buffer at pH 9.3 and sulfobutyl ether-β-cyclodextrin (2.5%, w/v) as chiral selector. The applied voltage was +30 kV, and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused-silica uncoated capillary with an id of 50 μm and total length of 60.0 cm. Under these conditions, a complete separation between IRD enantiomers was achieved in less than 7 min. Linearity was obtained in the range 50-300 μg/mL for both enantiomers (r≥0.9978). The RSD (%) and relative errors (%) obtained in precision and accuracy studies (intra-day and inter-day) were lower than 5%. Therefore, this method was found to be appropriate for controlling pharmaceutical formulations containing IRD enantiomers and the assay was considered to be stability indicating. The drug was subjected to oxidation, hydrolysis and photolysis. In all stress conditions the drug presented considerable degradation when compared with a fresh sample (zero time).     

Quantitation of cyclosporin A in whole blood by liquid chromatography/stable isotope dilution electrospray ionization mass spectrometry.

Therapy with cyclosporin A (CsA) for immunosuppression after organ transplantation requires monitoring of its levels in blood owing to the narrow therapeutic index of the drug and to the high inter-individual variability of the drug absorption and metabolism. We describe the preparation of CsA labelled with stable isotopes ((13)C and (2)H) with an isotopic enrichment of about 99% using labelled glucose and its use as internal standard for quantification of CsA blood levels by isotope dilution/electrospray ionization mass spectrometry. The method was found to be linear in the tested range (1-1000 ng) with and without the matrix. The accuracy of the bracketting calibration curves prepared using 100 ng ml(-1) labelled CsA was within +/-1.7% (bias). The results confirmed the usefulness of the procedure as a reference method for the external quality assessment of the field methods for the evaluation of CsA blood concentration, the imprecision (relative standard deviation) and accuracy (bias) being <2%.     

Cathodic adsorptive stripping square-wave voltammetric determination of nifedipine drug in bulk,pharmaceutical formulation and human serum

Nifedipine is a calcium-channel antagonist drug used in the management of angina pectoris and hypertension through inhibition of calcium influx. A fully validated sensitive cathodic adsorptive stripping square-wave voltammetry procedure was optimized for the determination of the drug at trace levels. The procedure was based on the reduction of the nitrophenyl group after the interfacial accumulation of the drug onto a hanging mercury drop electrode in Britton-Robinson buffer of pH 11.0. The optimal conditions of the procedure were found to be: accumulation potential=-0.9 V vs. Ag/AgCl/KCl(s)), accumulation time=30 s, scan increment=10 mV, pulse amplitude=50 mV and frequency=120 Hz. Under these conditions, a well-defined peak was obtained; its peak current showed a linear dependence on drug concentration in the range of 2x10(-9)-2x10(-7) mol L(-1) bulk nifedipine. The mean recoveries based on eight replicate measurements for 1x10(-8) and 5x10(-8) mol L(-1) bulk nifedipine solutions were 98.46+/-0.86% and 98.23+/-0.92%, respectively. A detection limit of 3.42x10(-10) mol L(-1) bulk nifedipine was achieved. The procedure was successfully applied for assay of the drug in tablets and spiked human serum with mean recoveries of 101.95+/-1.42% and 98.70+/-0.63%, respectively. The limit of detection of the drug in spiked human serum was found to be 3.90x10(-10) mol L(-1).     

Application of capillary zone electrophoresis with off-line solid-phase extraction to in vitro metabolism studies of antifungals

A simple and robust solid-phase extraction (SPE) procedure for the cleanup and sample preconcentration of antifungals (ketoconazole, clotrimazole, itraconazole, fluconazole, and voriconazole) and their metabolites after incubation with human liver microsomes, as well as a simplified capillary zone electrophoresis (CZE) method for their rapid analysis, have been developed to determine the stability of these compounds in in vitro samples. Three different sample pretreatment procedures using SPE with reversed-phase sorbents (100 mg C8, 100 mg C18, and 30 mg Oasis-HLB) were studied. The highest and most reproducible recoveries were obtained using a 30 mg Oasis-HLB sorbent and methanol containing 2% acetic acid as eluent. Enrichment by a factor of about four times was achieved by reconstituting the final SPE eluates to a small volume. For the CZE separation, good separations without interfering peaks due to the in vitro matrix were obtained with a simple running electrolyte using a fused-silica capillary. The best separation for all components originated by each tested drug after incubation with human liver microsomes (unmetabolized parent drug and its metabolites) was obtained using a 0.05 M phosphate running buffer (pH 2.2) without additives. The effect of the injection volume was also investigated in order to obtain the best sensitivity. Performance levels in terms of precision, linearity, limits of detection, and robustness were determined.     

Monitoring of total antimony and its species by ICP-MS and on-line ion chromatography in biological samples from patients treated for leishmaniasis

Results from a study are reported in which patients with leishmaniasis were monitored by whole blood, blood plasma, urine, and hair analysis, before, during, and after intramuscular administration of N-methyl meglumine antimoniate. Quadrupole ICP-MS was used for the detection of antimony and on-line ion chromatography for the separation of its species. After typically 30 consecutive daily injections of 5 mg antimony per kg of body weight, Sb concentrations of up to 250 microg L(-1) in whole blood and plasma, and 60 mg of Sb per gram of creatinine in urine, were measured 24 h after drug administration. Antimony in hair samples of these patients showed concentrations of up to 24 microg g(-1). Speciation studies of Sb5+ and Sb3+ in drug, urine, and plasma samples were performed by ion chromatography using a Hamilton PRP-100X anion exchange column and EDTA (2 or 20 mM, pH 4.7) as the mobile phases. Repeatability of elution time and peak area measurements for a 0.125 ng spike were <1.2% and <3.5%, respectively. Method detection limits for both species, using a 1:10 diluted urine or plasma sample, were typically 1.6 microg L(-1). The procedure was capable of separating the very intense drug peak from its inorganic species, thus permitting the first studies on the bio-transformation of N-methyl meglumine antimoniate to Sb5+ and Sb3+ in the human body.     

Flow injection spectrophotometric determination of isoproterenol using an avocado (Persea americana) crude extract immobilized on controlled-pore silica reactor

An enzymatic reactor was constructed by the immobilization of polyphenol oxidase (PPO) from avocado (Persea americana) crude extract in an inorganic support of controlled pore silica (CPS), after a previous step of silanization. This inorganic support has been used as an excellent carrier to immobilize this enzyme and the enzymatic reactor was used in a flow injection system for the determination of isoproterenol in pharmaceutical products. The procedure is based on the oxidation reaction of this drug with immobilized PPO and the product obtained was monitored at 492 nm. This system presented an analytical curve from 1.23x10(-4) to 7.38x10(-4) mol l(-1) isoproterenol with a detection limit of 6.25x10(-5) mol l(-1). Recoveries of isoproterenol between 98.5 and 103.1%, a relative standard deviation (R.S.D.) less than 1% (n=10) and 36 determinations per h were obtained.     

Direct enantiomeric resolution of disopyramide and its metabolite using chiral high-performance liquid chromatography. Application to stereoselective metabolism and pharmacokinetics of racemic disopyramide in man

A method for the simultaneous determination of disopyramide and mono-N-desisopropyldisopyramide enantiomers extracted from human plasma and urine is presented. Separation and quantitation were carried out using two columns coupled in series, and UV detection at 254 nm. First, the racemates of the two compounds were separated using a reversed-phase column, and then the enantiomers were separated using a stereoselective column packed with human alpha 1-acid glycoprotein. The mobile phase was 8 mM phosphate buffer, pH 6.20-2-propanol (92:8, v/v). The coefficients of variation (%) for the plasma daily determination were 6.7% for R(-)- and S(+)-disopyramide at drug levels of 1.5 micrograms/ml, and 8.5% and 7.7% for R(-)- and S(+)-mono-N-desisopropyldisopyramide, respectively, at drug levels of 0.375 micrograms/ml. The method has allowed the study of stereoselective metabolism and pharmacokinetics of disopyramide after oral administration as a racemate.     

Highly sensitive quantification of pemetrexed in human plasma using UPLC-MS/MS to support microdosing studies

Pemetrexed is an antifolate drug approved for the treatment of non-small-cell lung cancer and mesothelioma. Assessing pemetrexed pharmacokinetics after administration of a microdose (100 μg) may facilitate drug–drug interaction and dose individualization studies with cytotoxic drugs, without causing harm to patients. Therefore, a highly sensitive bioanalytical assay is required. A reversed-phase ultra-high performance liquid chromatography method was developed to determine pemetrexed concentrations in human ethylenediaminetetraacetic acid–plasma after microdosing. [¹³C₅]-Pemetrexed was used as the internal standard. The sample preparation involved solid-phase extraction from plasma. Detection was performed using MS/MS in a total run time of 9.5 min. The assay was validated over the concentration range of 0.0250–25.0 μg/L pemetrexed. The average accuracies for the assay in plasma were 96.5 and 96.5%, and the within-day and between-day precision in coefficients of variations was <8.8%. Extraction recovery was 59 ± 1 and 55 ± 5% for pemetrexed and its internal standard. Processed plasma samples were stable for 2 days in a cooled autosampler at 10°C. The assay was successfully applied in a pharmacokinetic curve, which was obtained as a part of an ongoing clinical microdosing study.     

Determination of Se using a solid-phase micro-extraction device coupled to a graphite furnace and detection by gas chromatography-mass spectrometry

A solid-phase micro-extraction (SPME) method using an SPME fiber device and graphite furnace (GF) for extracting Se compounds was proposed. Various factors affecting the derivatization and extraction of Se(IV) by SPME-GF were evaluated, including the effect of acid (type and concentration), the concentration of the derivatizing agent, the derivatization temperature, the extraction and derivatization times and the extraction temperature. After optimizing these conditions, the quantification of Se(IV) was performed by Gas Chromatography-Mass Spectrometry (GC-MS). The limit of detection was 0.37 μg L(-1) for Se(IV). The method was successfully applied to the total Se determination in certified reference materials (BCR-414 and SRM 1643e). A recovery of 97% was obtained for water (SRM 1643e). After microwave oven decomposition and the reduction of selenium using a mixture of 2 mol L(-1) HCl and 1% (w/v) KBr, a recovery of 101% and a relative standard deviation of 3.5% were attained for plankton (BCR-414). The SPME-GF method combined with GC-MS was also applied to the determination of the total selenium in a drug sample (selenium chelate).