Quantitative determination of potential genotoxic impurity 3-aminopyridine in linagliptin active pharmaceutical ingredient using HILIC–UV

This study aimed to develop an analytical method to determine the quantity of the impurity 3-aminopyridine (3AP). 3-Aminopyridine is a reactive reagent in the synthesis of linagliptin. The method was sensitive at level of 30.0 ppm of 3AP relative to linagliptin. The analysis was carried out using hydrophilic interaction liquid chromatography. The analytical column was Tracer Extrasil Silica (150 × 4.0 mm, 3 μm). A mobile phase of water–acetonitrile (10:90, v/v) containing 10.0 mM ammonium acetate was prepared and adjusted to pH 6.0. A UV detector was used to detect the amount of 3AP at a wavelength of 298 nm. Validation of the method was performed as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use in terms of detection limit, quantitation limit, linearity, accuracy, precision, specificity and robustness. The calibration curve was linear (r² = 0.999) for 3AP concentration in the range of 30.0–450.0 ppm. This method showed a good sensitivity with a detection limit and a quantitation limit of 7.5 and 25.0 ppm, respectively.     

Piezoectric Crystal Detection of Hydrogen Chloride Via Sulfur Dioide/Mercury Displacement

Abstract

Magnesium thiosulfate converts hydrogen chloride to sulfur dioxide, which then reduces mercurous ion to free mercury. This is detected as a mercurygold amalgam using a piezoelectric crystal detector. the reaction sequence has a response time of 2 minutes, is fully reversible, and is made specific for the analyte by the use of appropriate scrubber reagents placed before and after the magnesium thiosulfate. the detector has a linear response with a sensitivity of 8.3 Hz per ppm in the 0.5–92 ppm range, a relative standard deviation less than 5 percent, and an estimated limit of detection of approximately 20 ppb HCI.     

Ion Chromatography for Rapid and Sensitive Determination of Total Chlorine in Water

In this article, we report a new method that involves adsorption, oxygen bomb combustion, and ion chromatography for the preconcentration and determination of adsorbable organic halogen. This method can be divided into four steps, including: macroporous resin adsorption enrichment, optimization, oxygen bomb combustion, and ion chromatography determination. The project studies the macroporous resin adsorb organic halide pollutants and subsequent burn by an oxygen bomb combustion analyzer. The organic halogen in the aerobic environment combusts into hydrogen chloride. The water absorbing hydrogen chloride was then determined by ion chromatography. The influences of some adsorption and combustion parameters, such as the adsorption time, adsorption solution volume, solution pH, hexachlorobenzene acid concentration, combustion oxygen pressure, among others, on their respective adsorption efficiency were investigated. In the optimal condition, the adsorption time was 3.5 h; solution volume was 20 mL; pH was 4; combustion absorption time was 15 min; and the chloride calibration working range was from 1 ppm to 20 ppm (R ²  = 0.9998). Finally, the proposed method was successfully applied to the determination of organic halogen in water samples. The recoveries of chlorine (at spiked concentrations of 10 ppm and 20 ppm into water) in real samples ranged from 92.2% to 101.0%. Intra-day precision (N = 3) in terms of peak area, expressed as relative standard deviation, was found to be within the range of 0.68%–1.97%.     

A new method of analysis of peroxydisulfate using ion chromatography and its application to the simultaneous determination of peroxydisulfate and other common inorganic ions in a peroxydisulfate matrix

A new method for the determination of peroxydisulfate using ion chromatography has been developed. Elution of peroxydisulfate was effected by isocratic elution using 200 mM NaOH at 40°C. A modification of the method using gradient elution was able to simultaneously determine other common inorganic ions (nitrate, nitrite, sulfate and chloride) down to significantly low concentrations in a peroxydisulfate matrix. The relative standard deviations (RSD) were in the range of 0.5-5%, for peak areas and <0.2% for peak retention times. The recoveries were between 95% and 120% for a concentration range of about 0.5-42 ppm. The limit of detection for peroxydisulfate ion was 0.2 ppm and for the other ions were ≤2×10(-2) ppm. The calibration curves were linear with slope and intercepts close to 1 and 0, respectively.     

纳米MgO催化发光检测硫化氢

研究了硫化氢在纳米Mg O表面的催化发光现象,发现纳米Mg O对硫化氢具有较好的特异性,据此设计了硫化氢催化发光传感器。通过优化设计建立了一种快速检测硫化氢的新方法,线性范围为2.00~200ppm(r=0.999 3),检出限为0.8 ppm(信噪比S/N=3)。采用此传感器进行人工合成样品中硫化氢的加标回收分析,回收率为88.4%~97.2%。此传感器具有灵敏、快速、操作简便等优点,在硫化氢快速检测领域具有潜在应用前景。该文还探讨了硫化氢的催化发光反应机理。     

Gas chromatographic determination of tetramethylsuccinonitrile in poly(vinyl chloride) products in contact with food

A method is described for the determination of tetramethylsuccinonitrile (TMSN) in poly(vinyl chloride) (PVC) products in contact with food. TMSN was extracted from PVC with dichloromethane, steam distilled, extracted from the distillate with dichloromethane, then determined with a gas chromatograph equipped with a nitrogen-phosphorus detector and a 6-ft. glass column packed with Chromosorb W coated with 5% Thermon 1000 plus 0.5% phosphoric acid. Recoveries between 98.3 and 100.6% were obtained in the range of 0.5-12.5 ppm of TMSN by the use of nitrobenzene as an internal standard. The detection limit was 0.05 ppm of TMSN in 1 g of PVC products. The highest residue to TMSN found in PVC products in contact with food was 13.9 ppm.     

Monitoring Chloride and Nitrite Ions in 2,4-Dichlorofluorobenzene Plant Effluent by CE

A capillary electrophoresis method was developed for the separation and determination of chloride and nitrite in the effluents obtained during the process development of the synthesis of 2,4-dichlorofluorobenzene. Monitoring chloride and nitrite in the process effluents is necessary to improve the yield, minimize the formation of undesirable compounds and also to reduce environmental pollution. A buffer consisting of boric acid, chromate and tetradecyltrimethylammonium bromide was used for the separation. Nitrate was used as the internal standard. Indirect UV detection was performed at 254 nm using chromate co-ion as a chromophore. The limit of detection of chloride and nitrite were 0.85 and 1.05 ppm, respectively. The intra- and inter-day variance values were less than 3% with correlation coefficients for the two target anions of >0.999. The recoveries for chloride and nitrite ranged from 99.24% to 101.56%. Chlorides and nitrites in the process samples were in the range of 0.08–0.16% and 0.18–0.28%, respectively. There was no interference from other peaks under the optimized electrophoretic conditions.     

Determination of N,N-dimethylaminoethyl chloride and the dimethylaziridinium ion at sub-ppm levels in diltiazem hydrochloride by LC-MS with electrospray ionisation

An LC-MS method is described for the determination of the synthetic reagent N,N-dimethylaminoethyl chloride (DMC) in the drug substance diltiazem hydrochloride, for which the permissible limit is not more than 1 ppm (microgram g-1). The N,N-dimethylaziridinium ion (DMA), the reactive intermediate formed by cyclisation of DMC, is also detected. A column switching arrangement is used: diltiazem hydrochloride is trapped on a reversed-phase HPLC column, and the polar analytes are separated by ion exchange chromatography. Ionisation is effected by positive-ion electrospray, and the quadrupole filter mass spectrometer is operated in the selected ion recording mode. The detection limit (peak height-to-baseline noise ratio = 3) for DMC varies from day to day in the range < 0.05 to 0.1 ppm. The response for DMC is linear (r > 0.999) over the concentration range 0.2-10 ppm, and the repeatability is better than 7% (relative standard deviation) at 1.0 ppm. Concentrations of DMC in diltiazem hydrochloride from the manufacturing facility under study ranged from undetectable to about 0.07 ppm. An indirect TLC method has been published for the determination of DMC in mepyramine maleate, but it lacks the necessary sensitivity and specificity. The LC-MS method presented is direct, straightforward and suitable for routine use.     

Turbidimetric determination of sulphate in plant digests and natural waters by flow injection analysis with alternating streams

An improved flow injection system with alternating streams of reagents is described for the turbidimetric determination of sulphate. Samples are injected into an inert carrier stream which is mixed with barium chloride to form a barium sulphate suspension. The range of the method can be extended to low concentrations by continuously adding sulphate to the sample carrier stream. System performance is improved by automatic alternate pumping of the reagent stream and an alkaline EDTA solution at high flow rate. All operations are controlled by an electronically-operated proportional injector-commutator. Even after routine analysis of 3000 samples of natural waters and plant digests, baseline drift was not observed. The proposed method is suitable for 120 samples per hour with a relative standard deviation less than 1% for sulphate concentrations in the range 1–30 ppm (waters) or 5–200 ppm (plant digests). The results compare well with those obtained by standard manual procedures.     

Atomabsorptionsspektralphotometrische (A.A.S.) bestimmung von chrom in elektrodenkoks

A method is described for the determination of chromium in electrode-grade coke in the range 0·1–2 ppm (or 1–20 μg/ml in solution). The limit of detection is 0·4 μ/ml, the standard deviation is 0·008 absorbance units and the sensitivity is 0·02 absorbance units per μg. The influence of sulphuric acid and potassium hydrogen sulphate concentrations is discussed.     

High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Trospium Chloride in Human Plasma and Its Application in a Bioequivalence Study

A selective, rapid, and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed and validated for the quantification of trospium chloride in human plasma. With tramadol chloride as the internal standard, sample pretreatment involved a simple liquid-liquid extraction with chloroform-isopropyl alcohol (40/2, v/v) of 0.5 ml plasma. The analysis was carried out on a Hypsil C₁₈ column (150 mm × 2.1 mm, 5.0 μm) with a flow rate of 0.2 ml/min. The mobile phase was methanol-5% acetic acid-20 mM ammonium methylate (55/30/15, v/v/v). The detection was performed by a selected reaction monitoring (SRM) mode via electrospray ionization (ESI). Linear calibration curves were obtained in the concentration range of 0.2–50.0 ng/ml, with a lower limit of quantification of 0.2 ng/ml. The intra- and inter-day precision (RSD) values were below 15%. The method was successfully applied to a clinical bioequivalence study of trospium chloride in Chinese healthy volunteers following oral administration.     

Determination of captopril in human plasma with precolumn derivatization using solid phase extraction and HPLC

A rapid, accurate and sensitive method for the determination of captopril in human plasma was developed by solid phase extraction and high performance liquid chromatography (HPLC), using precolumn derivatization of captopril with chromophore label o-phethaldialdehyde (OPA). The extraction of captopril from human plasma was carried out by an amino propyl cartridge. A 0.01 M solution of HCl in methanol showed the best recovery and was chosen for elution of captopril in cartridge. This methanolic solution was applied to react with aqueous solution of OPA and glycine as a coderivatization reagent. The process of derivatization was completed within 2 min at room temperature. The derivatized captopril was injected into a reverse phase HPLC system. Mobile phase was consisted of water:acetonitrile:trifluoroacetic acid (85:15:0.1 v/v/v) with a flow rate of 1 ml min^?1 and detector was used at 345 nm. Linear dynamic range and limit of detection were found as 0.1–6 ppm and 0.1 ppm, respectively.     

Anion-exchange separation and spectrophotometric determination of vanadium in silicate rocks

A combined anion-exchange-spectrophotometric method has been developed for the determination of vanadium in silicate rocks. A rock sample weighing about 0.1 g is decomposed with a mixture of sulphuric and hydrofluoric acids and after removal of HF the residue is taken up with dilute sulphuric acid. This solution is adjusted to be 0.05M in sulphuric acid and contain 0.3% hydrogen peroxide, and is passed through a column of Amberlite CG 400 (sulphate form). The sorbed vanadium is eluted with 30 ml of 1M hydrochloric acid. The effluent is evaporated to dryness, made 0.1M in hydrochloric acid and 3% in hydrogen peroxide content, and passed through a column of Amberlite CG 400 (chloride form) to get rid of accompanying thorium and zirconium. Vanadium is stripped by elution with 20 ml of 1M hydrochloric acid and subsequently determined spectrophotometrically with 4-(2-pyridylazo)resorcinol. The detection limit is 0.4 ppm.     

Spectrofluorimetric Determination of Germanium Traces Using 1,2,4-Trihydroxyantraquinone

ABSTRACT

A new spectrofluorimetric method for determination of germanium traces based on its reaction with 1,2,4-Trihydroxyantraquinone, at an apparent pH 8.8 provided by an ammonia/ammonium chloride buffer, in a 80:20(v/v) ethyleneglycol water medium is proposed. The calibration graph is linear over the range 70–725 ng/ml and features a detection limit of 2.5 ng/ml. The effect of potential major interferences has been investigated and the proposed method was successfully applied to the determination of germanium in synthetic samples and industrial concentrates, after extraction with CCl₄, in an 9 M HCl medium.     

Extraction-spectrophotometric determination of tungsten with thiocyanate and some amidines

The procedure is based on reduction of W(VI) to W(V) by tin(II) chloride in 6 M hydrochloric acid, and extraction of the resultant thiocyanate complexes with a benzene solution of amidine. The complex coagulates and is dissolved in the benzene by addition of 1-pentanol. The maximum molar absorptivities of the complexes with 8 amidines in benzene/1-pentanol (9:1, v/v) are in the range 12 100–18 400 mol^?1 cm^?1. The simplest compound, N,N-diphenylbenzamidine gives the best sensitivity; the linear range covers 5–90 μg W in 10 ml of final solution; the detection limit is 2 ng W ml^?1. The method is applied to alloy steels.     

Determination of mercury in the presence of chloride by means of the ternary complex Hg(II)/xylenol orange/amberlite La-2 in non-aqueous media

The system Hg(II)/Xylenol Orange/Amberlite LA-2 dissolved in 1:1 v v 3-methylbutan-1-ol/chloroform medium has been studied. A 3:2:2 complex is formed, which is suitable for analytical measurements at temperatures <18 degrees . This complex allows the determination of mercury in the range 0.19-5.5 ppm with a molar absorptivity of 2.12 x 10(4).mole(-1).cm(-1) at 600 nm and extraction pH of 7.4 (standard deviation 0.065 ppm). The proposed method has been applied to the determination of mercury in contaminated water with a high chloride content.     

Spectrophotometric determination of aluminum in river water with bromopyrogallol red and n-tetradecyltrimethylammonium bromide by flow injection analysis

In the proposed flow injection system, the reagent solution contains bromopyrogallol red, n-tetradecyltrimethylammonium bromide and hexamine in 60% ethanolic solution, and the carrier solution contains acetate buffer, 1,10-phenanthroline and hydroxylammonium chloride. Sample solutions (160 μl) acidified by sulfuric acid are injected and the peak absorbance at 623 nm is recorded. The detection limit is about 0.001 ppm and calibration plots are linear for the ranges 0–0.3 and 0–0.1 ppm aluminum.     

Determination of nitrate in suspended particulate matter by high-performance liquid chromatography with u.v. detection

For the determination of nitrate in suspended particulate matter (s.p.m.), high-performance liquid chromatography (h.p.l.c.) with a u.v. detector at 210 mm gives precise and accurate results. Chloride, bromate, iodide, nitrite, thiocyanate and various cations do not interfere. Calibration graphs are linear over the range 0–20 ppm of nitrat-enitrogen, and the limit of detection is 0.25 ng of nitrate-nitrogen. The coefficients of variation at 5.0- and 10.0-ppm levels are 3.4 and 2.9%, respectively. Results obtained by the h.p.l.c. method and by two 2,4-xylenol spectrophotometric methods for aqueous extracts of s.p.m. are compared. Agreement is generally good, particularly when choride is removed in the 2,4-xylenol method, but the spectrophotometric methods are much more prone to interference.     

Studies on the stabilization of poly(vinyl chloride) with epoxides. Transformation products and their migration from packaging to foods

Epoxidized glyceryl trioleate has been used as a model compound to extend previous studies on the mode of action of epoxides in the stabilization of poly(vinyl chloride) (PVC). Sheets of PVC containing 3% expoxidized glyceryl tri[1-¹⁴C]oleate were prepared on a hydraulic press and subsequently heated in an oven for various times to simulate heat processing. After separation of the polymer from the low molecular weight components by steric exclusion chromatography, there was only a negligible amount (max. 2%) of bonding to the polymer and progressive loss from 15 to 90% of epoxide function occurred with heat processing over the period from 0.2 to 40 min. The concentration of the chlorohydrin transformation product was estimated by high performance steric exclusion chromatography after formation of a suitable u.v. detectable derivative, but the levels found did not fully account for the overall loss of epoxide. To assess the potential of both epoxide and chlorohydrin for migration from plastic packaging into foods, sheets individually containing the epoxide and the corresponding chlorohydrin were placed in contact with a range of solvents, orange squash and edible oil. No migration was measurable at a limit of detection of 0.1 ppm (orange squash limit 0.5 ppm) after 10 days contact at 40, with the exception of edible oil where a level of 1.0 ppm was detectable.     

Normal-phase high-performance liquid chromatographic determination of spiramycin in eggs and chicken

A precise method is presented for determination of residual spiramycin (SP) in chicken eggs and tissues by high-performance liquid chromatography (HPLC). The sample preparation was performed by homogenizing with a mixture of acetonitrile and n-hexane (5:4, v/v) to minimize the fat amount followed by ultra-filtration using a MolCutII(R). The extracts containing SP were free from interfering compounds when examined by the normal-phase HPLC using a LiChrosorb(R) NH(2) column and a mobile phase of acetonitrile-water (85:15, v/v) with a photo-diode array detector. The average recoveries from spiked SP (0.1, 0.5 and 1.0 ppm) were in excess of 89.0% with coefficients of variation between 1.4 and 2.4%. The limit of detection was 0.1 ppm.