Development of a voltammetric procedure for assay of the antihistamine drug hydroxyzine at a glassy carbon electrode: Quantification and pharmacokinetic studies

An electrochemical study of hydroxyzine at a glassy carbon electrode was carried out in the Britton-Robinson universal buffer of pH 2-11. Hydroxyzine was oxidized in a single two-electron irreversible process controlled mainly by adsorption. A simple, sensitive and time-saving square-wave adsorptive anodic stripping voltammetric procedure has been developed for determination of hydroxyzine in its commercial tablets and human serum without prior extraction. The optimized procedural conditions were: frequency=120Hz, scan increment=10mV, pulse-amplitude=25mV, accumulation potential=-0.3V, accumulation time=90-300s and a Britton-Robinson universal buffer of pH 4 as a supporting electrolyte. Mean recoveries of 100.5+/-0.71 and 98.6+/-1.12% (n=5) were achieved for assay of hydroxyzine in Atarax 10 and 25mg dosage forms, respectively. Limit of detection of 1.5x10(-8)molL(-1) (5.624ngmL(-1)) and limit of quantitation of 5.0x10(-8)molL(-1) (18.746ngmL(-1)) were achieved in human serum with a mean recovery of 98.4+/-1.22%, without prior extraction of the drug. Moreover, the described procedure was applied for evaluating the pharmacokinetic parameters of hydroxyzine in plasma of two healthy volunteers after administration of a single oral dose (Atarax)-25mg).     

Assay of dipyridamole in human serum using cathodic adsorptive square-wave stripping voltammetry

A rapid and sensitive square-wave voltammetric procedure was optimized for the determination of dipyridamole after its adsorption preconcentration onto a hanging mercury drop electrode. The peak current of the first of the two peaks developed for this drug in Britton-Robinson buffer at pH 8.0 has been considered for the present analytical study. An accumulation potential of -1.0 V versus Ag/AgCl/KCl(s), pulse amplitude a =100 mV, scan increment Delta E =10 mV, and frequency f =120 Hz were the optimal experimental parameters. Dipyridamole can be determined in the concentration range of 9.0 x 10(-9) to 5.0 x 10(-6) M using accumulation times of 30-300 s. A detection limit of 4.0 x 10(-11) M was achieved after a 300 s accumulation time. Applicability to serum samples was illustrated. The average recoveries for dipyridamole spiked to serum at 0.25-4.50 micro g ml(-1) were 96.0-102.0%, and the higher standard deviation was 2.9%. A detection limit of 0.06 micro g mL(-1) of serum was obtained.     

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).     

Determination of palladium(II) with alpha-(2-benzimidazolyl)-alpha',alpha'-(N-5-nitro-2-pyridylhydrazone)-toluene by adsorptive cathodic stripping voltammetry

The determination of palladium(II) complexed with alpha-(2-benzimidazolyl)-alpha',alpha'-(N-5-nitro-2-pyridylhydrazone)-Toluene (BINPHT) was investigated by adsorptive cathodic stripping voltammetry using hanging mercury drop electrode. Palladium(II) in the sample solution can be determined in BINPHT and ethylenediaminetetraacetic acid (EDTA). Accumulation is achieved by adsorption of Pd(II)-BINPHT complex on a hanging mercury drop electrode. Optimal conditions were found to be: supporting electrolyte; 0.01 M sodium acetate buffer at pH 5.0, accumulation potential; -590 mV versus Ag/AgCl, accumulation time; 180 s, scan rate; 50 mV s(-1), concentration of BINPHT; 2x10(-5) M. The linear range of Pd(II) was observed over the concentration range 20-100 ng ml(-1) The detection limit (S/N=3) is 2 ng ml(-1). A good reproductivity shows RSD of 2.0% (n=7). This procedure offers high selectivity with the presence of EDTA masking some metallic ions. River water sample spiking with palladium was determined.     

Simultaneous voltammetric determination of molybdenum and copper by adsorption cathodic differential pulse stripping method using a principal component artificial neural network

An adsorption differential pulse stripping method for the simultaneous determination of molybdenum and copper based on the formation of their complexes with cupferron (benzene, N-hydroxy-N-nitroso) is proposed. The optimum experimental conditions were obtained 0.010 mM cupferron, pH 3.0, accumulation potential of -0.15 V versus Ag/AgCl, accumulation time of 60 s, scan rate of 10 mV s(-1) and pulse height of 50 mV. Molybdenum and copper peak currents were observed at -0.16 and +0.02 V, respectively. A principal component artificial neural network (PC-ANN) was utilized for the analysis of the voltammogram data. A three layer back-propagation network was used with sigmoidal transfer function for the hidden and the output layers. The linear dynamic ranges were 5.0-60.0 and 0.1-20.0 ng ml(-1) for Cu(II) and Mo(VI), respectively. The detection limit was 0.06 ng ml(-1) for Mo(VI) and 0.20 ng ml(-1) for Cu(II). The capability of the method for the analysis of real samples was evaluated by the determination of molybdenum and copper in river water, tap water, and alloy.     

Quantification of terbutaline in pharmaceutical formulation and human serum by adsorptive stripping voltammetry at a glassy carbon electrode

The electrochemical oxidative behavior of terbutaline at the glassy carbon electrode was studied in a series of the Britton-Robinson buffer of pH 2--11. Cyclic and square-wave voltammograms of terbutaline at the pH values 相似文献   

Kinetic determination of iodide in pharmaceutical and food samples

A kinetic method for the determination of iodide based on its inhibitory effect on the Pd(III) catalysed reaction between ethylenediaminetetraacetic acid (EDTA)-Co(III) and the hypophosphite ion is described. The reaction was followed spectrophotometrically by measuring the decrease in the absorbance at 540 nm. Under the optimum experimental conditions of 2.6 x 10(-3) mol dm(-3)Co(III)-EDTA, 0.4 mol dm(-3)H2PO2-, pH 3.2 (adjusted with Britton-Robinson buffer), 0.57 micrograms ml(-1) Pd(III) and 20 +/- 0.2 degrees C, iodide was determined in the range 2-28 ng ml(-1). The method was applied to the determination of iodide in pharmaceutical products, iodinated salts, cow's milk and infants' powdered milk.     

Application of differential pulse stripping voltammetry and chemometrics for the determination of three antibiotic drugs in food samples

A reliable method for simultaneous determination of three antibiotic drugs(levofloxacin,gatifloxacin and lomefloxacin) by differential pulse stripping voltammetry(DPSV) in Britton-Robinson buffer(pH 7.96) was presented.The method is based on adsorptive accumulation of the antibacterial drugs on a hanging mercury dropping electrode(HMDE),followed by the reduction of the adsorptive species by the technique of DPSV.Optimal conditions,the deposition time of 80 s,the deposition potential of—1250 mV,and the scan rate of 25 mV/s,were obtained.The linear concentration ranges of 0.010-0.080μg/mL were obtained for all these three antibiotic drugs,while the detection limits were 2.38,3.20 and 1.60ng/mL for levofloxacin,gatifloxacin and lomefloxacin,respectively.In this work,chemometrics methods,such as classical least squares(CLS),partial least squares(PLS), principle component regression(PCR) and radial basis function-artificial neural networks(RBF-ANN),were used to quantitatively resolve the overlapping signals.It was found that PCR gave the best results with total relative prediction error(RPE_T) of 7.71%.The proposed method was applied to determine these three drugs in several commercial food samples with spiked method and yielded satisfactory recoveries.     

Determination of allura red in some food samples by adsorptive stripping voltammetry

Square wave (SW) voltammetry was used to explore the adsorption properties of the food additive dye Allura Red on a hanging mercury drop electrode (HMDE). By using the adsorptive stripping voltammetric approach, we developed a sensitive electroanalytical method for the determination of this azo dye. A well-developed voltammetric peak probably related to the cathodic reduction of the azo moiety was obtained in pH 9 Britton-Robinson (B-R) buffer at 613 mV. Cyclic voltammetric studies indicated that the reduction process was irreversible and primarily controlled by adsorption. The adsorptive voltammetric signal was evaluated with respect to various experimental conditions; the optimized values were supporting electrolyte, B-R buffer; pH 11; accumulation time, 180 s; accumulation potential, 0.0 V; scan rate, 900 mV/s; pulse amplitude, 75 mV; and SW frequency, 90 Hz. Adsorptive voltammetric peak current showed a linear response for Allura Red in the concentration range of 2.5 x 10(-8) to 2.0 x 10(-7) mol/L (r = 0.998). The limit of detection was 8.5 x 10(-9) mol/L (4.2 ng/mL), the precision in terms of relative standard deviation was 1.3%, and the mean recovery was 102%. Possible interferences by several substances usually present in food products such as food additive azo dyes (E110, E102), gelatin, natural and artificial sweeteners, preservatives, and antioxidants were also evaluated. The proposed electrochemical procedure was successfully applied to the determination of this food dye in commercially available candy and a soft drink. The results were compared by statistical evaluation with those obtained by a reference spectrophotometric method.     

Adsorptive Stripping Differential Pulse Voltammetry for Determination of Trace Amounts of Noscapine in Human Plasma

A new adsorptive anodic differential pulse stripping voltammetry method for the direct determination of noscapine at trace levels in human plasma of addicts is proposed. The procedure involves an adsorptive accumulation of noscapine on a hanging mercury drop electrode (HMDE), followed by oxidation of adsorbed noscapine by voltammetry scan using differential pulse modulation. The optimum conditions for the analysis of noscapine are pH = 8.5 using Britton‐Robinson (B‐R) buffer, accumulation potential of ?100 mV (vs. Ag/AgCl), and accumulation time of 150 s. The peak current is proportional to the concentration of noscapine, and a linear calibration graph is obtained at 0.015–2.75 μg mL^?1. A relative standard deviation of 1.28% (n = 5) was obtained, and the limit of detection was 7 ng mL^?1. The capability of the method for the analysis of real samples was evaluated by determination of noscapine in spiked human plasma and addicts, human plasma with satisfactory results.     

Differential pulse adsorption stripping voltammetric determination of copper(II) with 2-mercaptobenzimidazol at a hanging mercury-drop electrode.

Copper(II) was selectively accumulated on a hanging mercury-drop electrode by using 2-mercaptobenzimidazole. Ensuing measurements were carried out by differential pulse adsorption stripping voltammetry. Factors affecting the accumulation, reduction, and stripping steps were investigated and a procedure was developed. The optimum conditions for the analysis of copper were pH 5.0, 5.33 x 10(-5) M 2-mercaptobenzimidazole and an accumulation potential of -0.10 V (vs. Av/AgCl). A linear range was obtained in the concentration range 0.2-100 ng/ml with a 90 s accumulation time and a scan rate of 16 mV/s. For ten successive determinations of 1.0, 20.0 and 70.0 ng/ml copper(II), relative standard deviations of 4.2, 3.5 and 2.8%, respectively, were obtained. The developed method was applied to the determination of copper in commercial salts and aluminium alloys.     

Determination of cadmium in water by ICP-AES with on-line adsorption preconcentration using DPTH-gel and TS-gel microcolumns

Two flow injection inductively coupled plasma atomic emission spectrometric methods for the preconcentration and determination of trace amounts of cadmium in sea-water and waste-water samples are described based on the adsorption of the metal ion on a micro-column placed in the injection valve of the FI manifold and packed with silica gel funtionalised with 1,5-bis(di-2-pyridyl) methylene thiocarbohydrazide (DPTH-gel) and silica gel functionalised with methylthiosalicylate (TS-gel), respectively. Various parameters and chemical variables affecting the preconcentration and determination of this metal by ICP-AES are evaluated. The DPTH-gel preconcentration method has a linear calibration range from 5 to at least 100 ng ml(-1) of cadmium, with a R.S.D. of 1.1% for ten independent analyses of 100 ng ml(-1), a detection limit of 1.1 ng ml(-1) and a throughput of 40 samples per hour using a 60 s preconcentration time. The TS-gel preconcentration method shows a linear range between 10 and 100 ng ml(-1), with a R.S.D. of 2.5% for ten independent analyses of 100 ng ml(-1), a detection limit of 4.3 ng ml(-1) and a sample throughput of 24 samples per hour for a preconcentration time of 120 s. Validation was carried out against a certified reference water sample and by determining the analyte content in spiked synthetic sea-water, sea-water and waste-water.     

Simultaneous determination of the camptothecin analogue CPT-11 and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in cancer patients.

CPT-11 (I; 7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin) is a new anticancer agent currently under clinical development. A sensitive high-performance liquid chromatographic assay suitable for the simultaneous determination of I and its active metabolite SN-38 (II) in human plasma, and their preliminary clinical pharmacokinetics, are described. Plasma samples were processed using a solid-phase (C18) extraction step allowing mean recoveries of I, II and the internal standard camptothecin (III) of 84, 99 and 72%, respectively. The extracts were chromatographed on a C18 reversed-phase column with a mobile phase composed of acetonitrile, phosphate buffer and heptanesulphonic acid, with fluorescence detection. The calibration graphs were linear over a wide range of concentrations (1 ng/ml-10 micrograms/ml), and the lower limit of determination was 1 ng/ml for both I and II. The method showed good precision: the within-day relative standard deviation (R.S.D.) (5-1000 ng/ml) was 13.0% (range 4.9-19.4%) for I and 12.8% (6.7-19.1%) for II; the between-day R.S.D. (5-10,000 ng/ml was 7.9% (5.4-17.5%) for I and 9.7% (3.5-15.1%) for II. Using this assay, plasma pharmacokinetics of both I and II were simultaneously determined in three patients receiving 100 mg/m2 I as a 30-min intravenous infusion. The mean peak plasma concentration of I at the end of the intravenous infusion was 2400 +/- 285 ng/ml (mean +/- standard error of the mean). Plasma decay was triphasic with half-lives alpha, beta and gamma of 5.4 +/- 1.8 min, 2.5 +/- 0.5 h and 20.2 +/- 4.6 h, respectively. The volume of distribution at steady state was 105 +/- 15 l/m2, and the total body clearance was 12.5 +/- 1.9 l/h.m2. The maximum concentrations of the active metabolite II reached 36 +/- 11 ng/ml.     

Cathodic adsorptive stripping voltammetric determination of nalidixic acid in pharmaceuticals, human urine and serum

The quinolone antibacterial agent nalidixic acid (NAL) was studied by cyclic voltammetry (CV) and cathodic adsorptive stripping voltammetry (CASV). A sensitive method is described for the determination of NAL in its pure form, dosage forms and biological fluids. Controlled adsorptive accumulation of NAL on a hanging mercury drop electrode provides the basis for the direct stripping measurement of that compound in the nanomolar concentration level. Different variables were studied and optimized. The proposed method depends upon the voltammetric activity of NAL in Britton-Robinson buffer, whereby a well-defined cathodic peak is produced at pH 5.0 in presence of NO(3)(-). The calibration graph to determine NAL was linear in the range 7.4x10(-8)-2.5x10(-5) M by CASV. CAS voltammetry has been proved to be advantageous over a liquid chromatographic (LC) technique, allowing to detection limit signal to noise ratio, (s/n=3) of 0.766 ng ml(-1) (3.3x10(-9) M) NAL to be reached. The relative standard deviation (n=5) was 5.2% at concentration level of 1.0x10(-7) M NAL. The degree of interference from coexisting metal ions on the CASV signal for NAL was evaluated. The method was applied to two different commercial pharmaceutical products (Negram tablets and suspension) with very good recoveries. It was also shown that the method was successfully applied to the determination of NAL in human urine and blood serum. Mean recoveries were 98.8+/-0.3 and 98.9+/-0.41%, respectively.     

Square-wave anodic-stripping voltammetric determination of Cd, Pb, and Cu in a hydrofluoric acid solution of siliceous spicules of marine sponges (from the Ligurian Sea, Italy, and the Ross Sea, Antarctica)

Square-wave anodic-stripping voltammetry (SWASV) was set up and optimized for simultaneous determination of cadmium, lead, and copper in siliceous spicules of marine sponges, directly in the hydrofluoric acid solution (approximately 0.55 mol L(-1) HF, pH approximately 1.9). A thin mercury-film electrode (TMFE) plated on to an HF-resistant epoxy-impregnated graphite rotating-disc support was used. The optimum experimental conditions, evaluated also in terms of the signal-to-noise ratio, were as follows: deposition potential -1100 mV vs. Ag/AgCl, KCl 3 mol L(-1), deposition time 3-10 min, electrode rotation 3000 rpm, SW scan from -1100 mV to +100 mV, SW pulse amplitude 25 mV, frequency 100 Hz, DeltaE(step) 8 mV, t(step) 100 ms, t(wait) 60 ms, t(delay) 2 ms, t(meas) 3 ms. Under these conditions the metal peak potentials were Cd -654 +/- 1 mV, Pb -458 +/- 1 mV, Cu -198 +/- 1 mV. The electrochemical behaviour was reversible for Pb, quasi-reversible for Cd, and kinetically controlled (possibly following chemical reaction) for Cu. The linearity of the response with concentration was verified up to approximately 4 microg L(-1) for Cd and Pb and approximately 20 microg L(-1) for Cu. The detection limits were 5.8 ng L(-1), 3.6 ng L(-1), and 4.3 ng L(-1) for Cd, Pb, and Cu, respectively, with t(d) = 5 min. The method was applied for determination of the metals in spicules of two specimens of marine sponges (Demosponges) from the Portofino natural reserve (Ligurian Sea, Italy, Petrosia ficiformis) and Terra Nova Bay (Ross Sea, Antarctica, Sphaerotylus antarcticus). The metal contents varied from tens of ng g(-1) to approximately 1 microg g(-1), depending on the metal considered and with significant differences between the two sponge species.     

Application of adsorptive stripping voltammetry to the determination of the psychoactive drug temazepam in urine

Summary The influence of various operational parameters on the stripping response for temazepam is discussed. Interfacial and redox behaviour was also studied. 205 Ų was the average surface area per adsorbed molecule.The determination of temazepam in urine can be performed by using adsorption as a preconcentration step previous to its measurement at the hanging mercury drop electrode by differential pulse voltammetry in 0.01 mol/l Britton-Robinson buffer at pH 3.0 with a –0.50 V accumulation potential. The detection limit was 17 ng temazepam per ml of urine (15 s accumulation time) and the relative standard deviation was lower than 6.0% for 500 ng ml^–1 samples (10 s). The effects of various urine components on the voltammetric response have also been studied.

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Anwendung der adsorptiven Stripping-Voltammetrie zur Bestimmung des Psychopharmakons Temazepam in Urin

     

Determination of Bentazepam by differential pulse polarography and adsorptive stripping voltammetry

Summary A method is described for the determination of Bentazepam using DPP and ADSV with DP. Bentazepam is determined in buffer Britton-Robinson 0.04 mol l^-1 at pH 9 with detection limits of 3.1×10^-9 mol/l and a relative standard deviation of 0.8 DPP was used to determine Bentazepam in Tiadipona, the commercial product. ADSV was used to determine Bentazepam in urine with a detection limit of 2.7 ng ml^-1 (accumulation time 5 min) and a relative standard deviation of 1.5%.     

Study on the resonance Rayleigh scattering, second-order scattering and frequency doubling scattering spectra of the interactions of palladium(II)-ceftriaxone chelate with anionic surfactants and their analytical applications

In pH 1.8-2.9 Britton-Robinson (BR) buffer medium, ceftriaxone (CTRX) can react with palladium(II) (Pd(II)) to form 1:2 cationic chelate, which can further react with anionic surfactants (AS) such as sodium lauryl sulfonate (SLS), sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) to form 1:3 ion-association complexes. As a result, the resonance Rayleigh scattering (RRS), second-order scattering (SOS) and frequency doubling scattering (FDS) were enhanced greatly. The maximum RRS, SOS and FDS wavelengths of three ion-association complexes were located at 335 nm, 560 nm and 390 nm, respectively. The increments of scattering intensity (DeltaI) were directly proportional to the concentrations of CTRX in certain ranges. The detection limits (3sigma) of CTRX for SLS, SDBS and SDS systems were 1.8 ng ml(-1), 2.3 ng ml(-1) and 2.3 ng ml(-1) (RRS method), 4.9 ng ml(-1), 7.4 ng ml(-1) and 4.7 ng ml(-1) (SOS method) and 6.8 ng ml(-1), 7.3 ng ml(-1) and 9.1 ng ml(-1) (FDS method), separately. The sensitivity of RRS method was higher than those of SOS and FDS methods. The optimum conditions of RRS method and the influence factors were investigated, and the composition of ion-association complexes and the reaction mechanism were discussed also. The effects of foreign substances were tested and it showed that the method has a good selectivity. Based on the ion-association reaction, the sensitive, simple and rapid methods for the determination of CTRX have been developed.     

A sensitive and selective liquid chromatographic/electrospray ionization tandem mass spectrometric assay for the simultaneous quantification of alpha-,beta-arteether and its metabolite dihydroartemisinin in plasma,useful for pharmacokinetic studies

A sensitive, selective, specific and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric assay method was developed and validated for the simultaneous quantitation of alpha-,beta-arteether (alpha-,beta-AE) and its metabolite alpha-dihydroartemisinin (DHA) in monkey plasma using the propyl ether analogue of beta-arteether (PE) as an internal standard. The method involves a simple two-step liquid-liquid extraction with hexane. The analytes were chromatographed on a C(18) reversed-phase chromatographic column by isocratic elution with methanol-ammonium acetate buffer (pH 4) (92 : 8, v/v) and analysed by mass spectrometry in the multiple reaction monitoring mode. The chromatographic run time was 7 min and the weighted (1/x(2)) calibration curves were linear over the range 0.78-200 ng ml(-1). The method was validated in terms of accuracy, precision, absolute recovery, freeze-thaw stability, bench-top stability and re-injection reproducibility. The limit of detection and lower limit of quantification in monkey plasma were 0.39 and 0.78 ng ml(-1) respectively for all the analytes. The intra- and inter-batch precision and accuracy were found to be well within acceptable limits (<15%). All three analytes were stable even after three freeze-thaw cycles (deviation < 15%). The average absolute recoveries of alpha-,beta-AE, DHA and PE, used as an internal standard, from spiked plasma samples were 85.85 +/- 6.56, 70.10 +/- 7.06, 54.37 +/- 3.39 and 93.90 +/- 6.9%, respectively. The assay method described here could be applied to study the pharmacokinetics of alpha-,beta-AE and DHA in rhesus monkeys.     

Square-wave adsorptive cathodic stripping voltammetric determination of anti-inflammatory indomethacin drug in tablets and human serum at a mercury electrode

Indomethacin is a non-steroidal anti-inflammatory drug possessing anti-pyretic and analgesic properties. A fully validated square-wave adsorptive cathodic stripping voltammetric procedure is described for determination of indomethacin. The procedure was based on the reduction of the C=O double bond of the drug molecule in Britton-Robinson buffer (pH 4) after its preconcentration onto the mercury electrode surface. The optimized conditions of the procedure were: frequency 120 Hz, scan increment 10 mV, pulse amplitude 50 mV, preconcentration potential -0.9 V (vs. Ag/AgCl/KCl(s)) and preconcentration time 90 s. The proposed procedure was successfully applied for determination of the drug in tablets and human serum with good recoveries. The limits of detection in bulk form and human serum were 6.7 x 10(-10) mol L(-1) and 8.1 x 10(-10) mol L(-1), respectively.