Low-Level (PPB)Determination of Cisplatin in Cleaning Validation (Rinse Water) Samples. II. A High-Performance Liquid Chromatogrphic Method

A high-performance liquid chromatographic (HPLC) method is described for the determination of residual levels of cisplatin from extracts of surfaces with very low surface area; from extracts of surfaces of coupons made of Teflon® (polytetrafluoroethylene, PTFE), stainless steel, and glass; and in aqueous solution collected after rinsing equipment and parts. Initially, the method was developed to determine cisplatin at concentrations ranging from 20 to 200 ng/ml by direct injection. Retaining the same method conditions, the scope of the method was expanded by the addition of a sample preconcentration step, allowing analyses at levels ranging from 0.5 ng to 20 ng/ml. Preconcentration is necessary for the determination of cisplatin in rinse waters at a quantifiable concentration of about 2 PPB. Under these conditions, the detection limit is about 0.2 to 0.3 ng/ml. Residual cisplatin on different types of surfaces, including surfaces with very low surface area, can be determined by swabbing each test surface with a derivatizing solution. The cisplatin recovered in the swabbing solution can be analyzed by HPLC using direct injection or preconcentration, depending on the expected level of cisplatin in the sample. Initial methods were developed to quantitate at a cisplatin concentration of about 100 PPB or higher in solution extracted from surfaces. However, when surface areas are limited because of the size of the parts, solution concentration becomes very low as a result of the minimum volume required for extraction. To support the application of swabbing techniques to surface analysis, stainless steel, Teflon, and glass surfaces were spiked with cisplatin at 2.5 to 20 ng/cm². Satisfactory overall recoveries of 90% ± 10% were obtained from all surfaces. Cisplatin has no ultraviolet/visible (UV/Vis) spectral-active functional group that can be used to detect low levels of cisplatin. Hence, diethyldithiocarbamate (DDTC) was used as a derivatizing agent to increase sensitivity to UV absorption at 340 nm. Diethyldithiocarbamate forms complexes with the platinum in cisplatin to yield a platinum-DDTC (Pt-DDTC) complex with a high molar-extinction coefficient. The Pt(DDTC)² complex thus formed was chromatographically separated and then quantitated by comparison of its detector response to that of a similarly derivatized standard preparation. DDTC also has application as a cleaning agent for cisplatin (e.g., for production equipment cleaning, spill cleanup). Destruction of cisplatin can be effected by the reaction of cisplatin with this cleaning agent. Derivatization of cisplatin will convert active cisplatin to platinum-DDTC on surfaces or in solution. Final cleaning can be accomplished using a water-for-injection rinse. After such a cleaning process, the rinse water, when collected and analyzed, showed levels of free cisplatin less than the detection concentration of 0.2 PPB and a total platinum concentration less than 10 PPB as Pt-DDTC complex.     

Low-level (PPB) determination of cisplatin in cleaning validation (rinse water) samples. I. An atomic absorption spectrophotometric method

Suitable analytical methods are required for quantitative determination of trace levels of ingredients in samples obtained for purposes of cleaning validation. We describe below an atomic absorption method for the quantitation of cisplatin, an antineoplastic agent, in aqueous samples. Cisplatin was reacted with diethyldithiocarbamic acid (DDTC), sodium salt, to yield a platinum-DDTC (Pt-DDTC) complex. The Pt-DDTC chelate was extracted into methylene chloride, the extract was mixed with acetonitrile, and the platinum content was then determined using a Zeeman atomic absorption (AA) spectrophotometer. The extraction conditions and AA experimental conditions were set up such that the detection level could be extended to 0.5 ng/ml. Reproducible results were obtained at a quantitative working standard concentration of 5 PPB. The absorbance response was found to be a linear function of cisplatin concentration in the region between 0.5 PPB and 20 PPB, which is about 10% to 400% of the target analyte concentration of 5 PPB. The target analyte concentration was set at 5 PPB such that it was at least 10 times the detection limit of about 0.5 PPB.     

Chemical suppression of contaminant metal ions using a metastable state in precolumn derivatizing HPLC: an ultratrace fluorometric detection of Al(III)

The contamination of metal ions from reagents used frequently restricts the practical detection limit of the metal ion, which itself is a source of contamination. We have found a novel solution to this problem, a chemical-suppressing method of contaminant metal ions on a reversed-phase HPLC for Al3+ with a detection limit of 7.6 x 10(-11) mol dm(-3) (2.1 ng dm(-3)) by only adding a certain agent into all stock solutions without any preconcentration or purification steps. This technique decreases the concentration of the contaminant Al3+ originating from the reagents by more than 1 order of magnitude using selective derivatization of sample Al3+ ions to a powerful fluorescent complex at a metastable state in the precolumn chelation processes. Meanwhile, the contaminant Al3+ remains as a nonfluorescent complex with a blocking reagent in order to suppress the contamination. This selective derivatization is achieved by the accumulation of several complexation processes based on the difference of formation, dissociation, and ligand-exchange kinetics and the thermodynamics between the derivatizing reagent, the 4',5'-geometorical isomer of calcein, and the blocking reagent, o,o'-dihydroxyazobenzene. This simple and smart HPLC system was validated through recovery tests of environmental and biological samples.     

Optimization of the preconcentration system of cadmium with 1(2-thiazolylazo)-p-cresol using a knotted reactor and flame atomic absorption spectrometric detection

The present paper proposes an on-line preconcentration procedure for cadmium determination in drinking water samples. It is based on the precipitation of cadmium(II) ions on a knotted reactor (KR) using 1(2-thiazolylazo)-p-cresol (TAC) as complexing reagent. The optimization step was performed using a full factorial design involving the variables: pH, eluent concentration (nitric acid) and TAC concentration. The results of this experiment demonstrated that these variables at chosen levels are not statistically significant. Under optimized experimental established conditions, analytical parameters for the preconcentration method were: a detection limit of 40.0 ng/l, precision as relative standard deviation (RSD) of 1.2 and 1.0%, for cadmium concentration of 2.5 and 20.0 microg/l, respectively. The preconcentration factor considering the slopes of the analytical curves with and without preconcentration is 23 for a sample volume of 10 ml. This system shows a sampling frequency of 25 h(-1). In order to check the accuracy, the standard reference material, NIST SRM 1643d trace elements in water was analyzed. A comparison, using t-test demonstrates that there is not significant difference among the achieved results with proposed method and the certified values. The addition/recovery experiments in the samples analyzed demonstrated the accuracy and applicability of the system developed for cadmium determination in water samples.     

Selective measurement of ultratrace methylmercury in fish by flow injection on-line microcolumn displacement sorption preconcentration and separation coupled with electrothermal atomic absorption spectrometry

A novel nonchromatographic speciation technique for ultratrace methylmercury in biological materials was developed by flow injection microcolumn displacement sorption preconcentration and separation coupled on-line with electrothermal atomic absorption spectrometry (ETAAS). In the developed technique, Cu(II) was first on-line complexed with diethyldithiocarbamate (DDTC), and the resultant Cu-DDTC was presorbed onto a microcolumn packed with the sorbent from a cigarette filter. Selective preconcentration of methylmercury (MeHg) in the presence of Hg(II), ethylmercury (EtHg), and phenylmercury (PhHg) was achieved at pH 6.8 through loading the sample solution onto the microcolumn due to a displacement reaction between MeHg and the presorbed Cu-DDTC. The retained MeHg was subsequently eluted with 50 microL of ethanol and on-line determined by ETAAS. Interferences from coexisting heavy metal ions with lower stability of their DDTC complexes relative to Cu-DDTC were minimized without the need of any masking reagents. No interferences from 5.5 mg L(-1) Cu(II), 4.5 mg L(-1) Cd(II), 2.5 mg L(-1) Cr(III), 3 mg L(-1) Fe(III), 10 mg L(-1) Ni(II), 10 mg L(-1) Pb(II), and at least 25 mg L(-1) Zn(II) were observed for the determination of MeHg at the 50 ng L(-1) level (as Hg). With the consumption of only 3.4 mL of sample solution, an enhancement factor of 75, a detection limit of 6.8 ng L(-1) (as Hg) in the digest (corresponding to 3.4 ng g(-1) in original solid sample for a final 50 mL of digest of 0.1 g of solid material), and a precision (RSD, n = 13) of 2.3% for the determination of methylmercury at the 50 ng L(-1) (as Hg) level were achieved at a sample throughput of 30 samples h(-1). The recoveries of methylmercury spike in real fish samples ranged from 97 to 108%. The developed technique was validated by determination of methylmercury in a certified reference material (DORM-2, dogfish muscle), and was shown to be useful for the determination of methylmercury in real fish samples.     

Imaging of metal ion dissolution and electrodeposition by anodic stripping voltammetry-scanning electrochemical microscopy

We have developed a new imaging method for scanning electrochemical microscopy (SECM) employing fast-scan anodic stripping voltammetry (ASV) to provide sensitive and selective imaging of multiple chemical species at interfaces immersed in solution. A rapid cyclic voltammetry scan (100 V/s) is used along with a short preconcentration time (300-750 ms) to allow images to be acquired in a normal SECM time frame. A Hg-Pt film electrode is developed having an equivalent Hg thickness of 40 nm that has good sensitivity at short preconcentration times and also retains thin-film behavior with high-speed voltammetric stripping. Fast-scan anodic stripping currents are shown to be linear for 1-100 microM of Pb (2+) and Cd (2+) solutions using a preconcentration time of 300 ms. SECM images showing the presence of Pb (2+) and Cd (2+) at concentrations as low as 1 microM are presented. In addition, a single ASV-SECM image is shown to produce unique concentration maps indicating Cd (2+) and Pb (2+), generated in situ from a corroding sample, while simultaneously detecting the depletion of O 2 at this sample. The transient voltammetric response at the film electrode is simulated and shows good agreement with the experimental behavior. We discuss the behavior of images and concentration profiles obtained with different imaging conditions and show that mass-transport limitations in the tip-substrate gap can induce dissolution. ASV-SECM can thus be used to detect and study induced dissolution not only at bulk metal surfaces but also on underpotential deposition layers, in this case Cd and Pb on Pt. In addition, we discuss how surface diffusion phenomena may relate to the observed ASV-SECM behavior.     

The application of atomic absorption spectrometry for the determination of residual active pharmaceutical ingredients in cleaning validation samples

The objective of this work was the development and validation of atomic absorption spectrometric (AAS) methods for the determination of residual active pharmaceutical ingredients (API) in rinse samples for cleaning validation. AAS as an indirect method for the determination of API in rinse samples can be applied when it is in the form of salt with metal ions or when the metal ion is a part of the API's structure. The electrothermal AAS methods (aqueous and ethanol medium) for the determination of magnesium in esomeprazole magnesium and the flame AAS method for the determination of lithium in lithium carbonate in rinse samples were developed. Various combinations of solvents were tested and a combination of 1% aqueous or ethanol solution of nitric acid for esomeprazole magnesium and 0.1% aqueous solution of nitric acid for lithium carbonate were found to be the most suitable. The atomization conditions in the graphite furnace and in the flame were carefully studied to avoid losses of analyte and to achieve suitable sensitivity. The cleaning verification methods were validated with respect to accuracy, precision, linearity, limit of detection, and quantification. In all the cases, the limits of detection were at the microgram level. The methods were successfully applied for the determination of esomeprazole magnesium and lithium carbonate in rinse samples from cleaning procedures.     

In situ comparative studies of self-assembly adsorption of bovine serum albumin on nano films by atomic force microscopy

The self-assembly adsorption of function protein on crystal surfaces, as a common phenomenon, broadly takes place in many applications of biosensors, biocapsules and bioMEMS/bioNEMS. To systematically investigate the different adsorption characteristic of the same function protein on two different crystal surfaces under the identical environment, a hybrid surface composing silica and discontinuous Gold Nano Film (GNF) was fabricated by Physical Vapor Deposition (PVD) and ultrasonic cleaning method, where the dynamic process of the self-assembly adsorption of Bovine Serum Albumin (BSA) was in situ observed by Atomic Force Microscope (AFM). The variations on the junction area of the two different surfaces were studied in the aqueous solution before and after injecting BSA with 0.05 mg/ml concentration. It was found that silica, compared with same hydrophilic GNF, took on a fairly weak adsorption force. The results indicated that the adsorption strength of BSA on the hydrophilic crystal surface was determined not only by hydrophilic property, but also other interaction forces, like Van der Waals and so on. Moreover, observed under the contact mode of AFM, BSA adsorbed on GNF had great tendency to forming a ridge-like topography. These results may be helpful in the application of immunosensors and other areas.     

有色金属表面水基原油清洗剂的研制

通过对数十种表面活性剂对原油的溶解情况观察,筛选出几种溶解效果较好的表面活性剂进行复配,通过大量的正交实实验,确定出水基原油清洗剂的配方。研究了静态条件下脱脂温度和脱脂时间对除油效果的影响,并对其它性能进行了评价。研制的有色金属表面水基原油清洗剂,主要用于多种金属外表面的原油清洗。结果表明,该清洗剂具有去污能力强,常温清洗效果好,对金属腐蚀小,环境污染小,成本低等特点。     

Solid phase extraction method for selective determination of Pb(II) in water samples using 4-(4-methoxybenzylidenimine) thiophenole

A sensitive and selective extractive preconcentration procedure for the determination of traces of lead in water samples has been developed. An alumina-sodium dodecyl sulfate (SDS) coated modified with 4-(4-methoxybenzylidenimine) thiophenole (MBITP) was used for preconcentration and determination of Pb(II) by flame atomic absorption spectrometry. Lead was adsorbed quantitatively on modified column due to its complexation with MBITP and quantitatively eluted using 5 mL 1 mol L(-1) nitric acid in acetone. The effects of parameters such as pH, amount of solid phase, amount of MBITP, flow rate, type and concentration of eluting agent were examined. The effect of interfering ions on the determination of Pb(II) was also investigated. The response of proposed method is linear in the concentration range 0.05-1.2 microg mL(-1) of Pb(II). The limit of detections (3S.D.(b)/m, n=4) and relative standard deviations (n=11) are 1.6 ng mL(-1) and 0.9%, respectively. The presented procedure was successfully applied for determination of lead content in real samples such as river, spring, waste and drinking water.     

Selective mercury determination after membrane complexation and total reflection X-ray fluorescence analysis

A new method for low mercury concentration analysis in drinking waters is presented. Membranes containing a few micrograms of various complexing reagents were produced on the surface of quartz glasses (reflectors). The reflectors were immersed in water solutions containing various concentrations of inorganic mercury salts at low concentrations (1-40 ng/mL). The membranes were left to equilibrate in 5-500 mL of solution for many hours; when the equilibration stage was finished they were cleaned with ultrapure water and left to dry. Analyses were performed by total reflection X-ray fluorescence (TXRF). The effects of various experimental parameters (complexing agent, equilibrium time, sample volume, etc.) as well as the selectivity of the membranes were studied. The complexing reagent dithizone with a PVC-based membrane gave the best results. The limit of quantitation was 0.8 ng/mL.     

Blood response to plasticized poly(vinyl chloride): dependence of fibrinogen adsorption on plasticizer selection and surface plasticizer level

The high level of plasticizer in plasticized poly(vinyl chloride) (PVC) ensures that plasticizer selection has an important influence on the suitability of PVC to function in blood-contacting applications. In this study, three types of plasticized PVC in sheet form, with di-(2-ethylhexyl)phthalate (DEHP), tri-(2-ethylhexyl)trimellitate (TEHTM) and n-butyryltri-n-hexyl citrate (BTHC) as plasticizer, were selected for assessment and single solute fibrinogen adsorption was utilized as an initial index of interactions with blood components. Fibrinogen adsorption behavior shows a strong dependence on the plasticizer selection, plasticizer level at the surface and the adsorption conditions, such as adsorption time and fibrinogen solution concentration. Results indicate that BTHC plasticized PVC possesses the lowest adsorption capacity in the three types of plasticized PVC, while TEHTM plasticized PVC seems to have the strongest reactivity in certain fibrinogen solution concentrations. The alteration of surface plasticizer level was achieved by a methanol-cleaning treatment with a variety of cleaning times and the fibrinogen adsorption on plasticized PVC decreases with the reduction of surface plasticizer level. The migration behavior of two phthalate esters (DEHP and TEHTM) was evaluated using UV-Spectrophotometer to determine the plasticizer level at the surfaces. In addition, the fibrinogen adsorption mechanism was examined with Freundlich adsorption modeling.     

Determination of lead in human saliva by combined cloud point extraction-capillary zone electrophoresis with indirect UV detection

A micelle-mediated phase separation without added chelating agents to preconcentrate trace levels of lead in human saliva as a prior step to its determination by capillary electrophoresis has been developed. The enrichment step is based on the cloud point extraction of lead with the non-ionic surfactant PONPE 7.5 in the absence of chelating agent. The surfactant-rich phase was diluted with acetonitrile and the resultant solution was injected directly into the CE instrument. Factors affecting the combined methodology such as surfactant-rich phase diluting agent, buffer pH and concentration, applied voltage, sample preparation and presence of additives were studied in detail. A BGE of 20 mM imidazole containing 30% acetonitrile, pH 6.20 was found to be optimal for the separation of lead from other saliva constituents. Indirect detection was performed at 205 nm. The detection limit value of lead for the preconcentration of 8 ml of saliva was 11.4 microg l(-1). The calibration graph using the preconcentration system was linear with a correlation coefficient of 0.997 at levels near the detection limits up to at least 400 microg l(-1). The reproducibility (R.S.D.) on the basis of migration time and peak area were better than 0.68 and 3.6%, respectively. The method was successfully applied to the determination of lead in human saliva.     

环保型金属清洗剂的研制及其清洗效果

研制环保型水基金属清洗剂是水基清洗剂的发展方向。为此,选择了几种具有高效生物降解性的表面活性剂,并将其复配,采用表面张力测定及称重法考察了单一型及复配型体系对金属清洗的效果及效率。结果显示：清洗剂配方为m[APGC8-10（烷基糖苷）]：m[AEO-9（C12脂肪醇聚氧乙烯醚）]=1：1,浓度为3g／L,以Na2CO3...     

Chemistry and structure of GaAs surfaces cleaned by sulfur annealing

A new method for cleaning and passivating GaAs surfaces, sulfur annealing, is proposed. The GaAs surfaces are exposed to sulfur atoms generated by an Ag/AgI/Ag₂S/Pt electrochemical cell at elevated substrate temperatures without arsenic beam irradiation. The chemistry and structure of the GaAs surfaces cleaned by sulfur annealing are studied by synchrotron radiation photoemission spectroscopy and low energy electron diffraction (LEED). The S 2p and Ga 3d spectra indicate that Ga---S bonds are formed on the GaAs surfaces where no oxides remain. 4 × 1 and 2 × 1 LEED patterns were observed for the surfaces with an average sulfur layer thickness of 0.15 nm and 0.24 nm respectively. The surface band bending is found to be reduced by 0.2–0.3 eV for the sulfur-annealed surfaces, but slightly increased for the conventionally cleaned surfaces with arsenic beam irradiation. We conclude that the surface cleaning and the submonolayer sulfur passivation can be attained simultaneously by sulfur annealing without arsenic beam irradiation. The method is promising for pre-cleaning the GaAs surfaces before semiconductor crystal growth and thin film deposition.     

Determination of Co(II) in water and soil samples using spectrophotometry coupled with preconcentration on 4-amino methyl pyridine anchored silica gel column

4-amino methyl pyridine anchored silica gel (4-AMPS) was used as a sorbent in a simple sensitive spectrophotometry determination of Co(II) in various samples using piperazine dithiocarbamate as a color developing agent (lambda(max)=390 nm) at pH 5.0+/-0.2. Beer's law was obeyed over the range of 0.1-5.0 microg ml(-1). The molar absorptivity and Sandell's sensitivity were 1.257x10(5) lmol(-1) cm(-1) and 0.006145 microg cm(-2), respectively. Under these conditions, the preconcentration factor obtained was 80, and the detection limit achieved was 5.0 ng ml(-1). The detailed study of various interfering ions made the method more sensitive and selective. The recovery of Co(II) from various samples range from 97.50 to 99.66%. The present method was successfully applied for the determination of Co(II) in various water and soil samples. The proposed method was compared with reported methods in terms of Student's 't'-test and variance ratio 'f'-test which indicates that there is no significant difference between proposed and literature method at 95% confidence level.     

Simultaneous separation/preconcentration of ultra trace heavy metals in industrial wastewaters by dispersive liquid-liquid microextraction based on solidification of floating organic drop prior to determination by graphite furnace atomic absorption spectrometry

In the present work, an efficient microextraction method was applied to separation and preconcentration of Ni(II), Co(II), Pb(II) and Cr(III). This method is dispersive liquid-liquid microextraction based on solidification of floating organic drop, which overcomes the most important problems of each aforementioned technique. The influences of analytical parameters, including pH, extraction solvent volume, disperser solvent type and its volume, concentration of chelating agent, salt effect and extraction time on the quantitative recoveries of nickel, cobalt, lead and chromium ions were investigated. Under the optimized conditions, the limits of detection were 0.2 ng L(-1) for Cr and 1.3 ng L(-1) for Co, Ni and Pb, with a preconcentration factor of 800 times. The relative standard deviations of 6.2% at 6.0 ng L(-1) of Cr and 7.2% at 10 ng L(-1) of Co, Ni and Pb were obtained (n=7). The proposed method was successfully applied for the analysis of ultra trace metals in water and wastewater samples.     

20碳钢水基清洗剂的配制及应用效果

为了洗净量大面广的钢铁制品表面的防锈油,配制了一种有效的20碳钢水基清洗剂。采用单因素试验法,逐一对5种市售非离子表面活性剂进行了除油清洗,优选出表面活性剂(脂肪醇聚氧乙烯醚)后,确定PAA分散剂、助剂和缓蚀剂的最佳含量。按照国标分别采用DDS-307A电导仪、722N可见分光光度计测定清洗剂的临界胶束浓度和浊点。结果表明:20碳钢水基清洗剂的最佳组成为4 g/L 087型表面活性剂,3 g/L 731分散剂,12 g/L无水碳酸钠,4 g/L硅酸钠,1~2 g/L十二烷基硫酸钠。本清洗剂碱度小、耐酸性好、除油效果能满足生产需要。     

Surface cleaning and etching of 4H-SiC(0001) using high-density atmospheric pressure hydrogen plasma

We propose low-damage and high-efficiency treatment of 4H-SiC(0001) surfaces using atmospheric pressure (AP) hydrogen plasma. Hydrogen radicals generated by the AP plasma was found to effectively remove damaged layers on SiC wafers and improve surface morphology by isotropic etching. Localized high-density AP plasma generated with a cylindrical rotary electrode provides a high etching rate of 1.6 microm/min and yields smooth morphology by eliminating surface corrugation and scratches introduced by wafer slicing and lapping procedures. However, high-rate etching with localized plasma was found to cause an inhomogeneous etching profile depending on the plasma density and re-growth of the poly-Si layer at the downstream due to the decomposition of the vaporized SiH(x) products. On the other hand, for the purpose of achieving moderate etching and ideal cleaning of SiC surfaces, we demonstrated the application of a novel porous carbon electrode to form delocalized and uniform AP plasma over 4 inches in diameter. We obtained a reasonably moderate etching rate of 0.1 microm/min and succeeded in fabricating damage-free SiC surfaces.     

Determination of trace aluminum in biological and water samples by cloud point extraction preconcentration and graphite furnace atomic absorption spectrometry detection

A cloud point extraction (CPE) method for the preconcentration of trace aluminum prior to its determination by graphite furnace atomic absorption spectrometry (GFAAS) has been developed. The CPE method is based on the complex of Al(III) with 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP), and then entrapped in non-ionic surfactant Triton X-114. PMBP was used not only as chelating reagent in CPE preconcentration, but also as chemical modifier in GFAAS determination. The main factors affecting CPE efficiency, such as pH of sample solution, concentration of PMBP and Triton X-114, equilibration temperature and time, were investigated in detail. An enrichment factor of 37 was obtained for the preconcentration of Al(III) with 10 mL solution. Under the optimal conditions, the detection limit of this method for Al(III) is 0.09 ng mL(-1), and the relative standard deviation is 4.7% at 10 ng mL(-1) Al(III) level (n=7). The proposed method has been applied for determination of trace amount of aluminum in biological and water samples with satisfactory results.