Alkaline Degradation Products Research Articles

Simultaneous determination of sulpiride and its alkaline degradation product by second derivative synchronous fluorescence spectroscopy

Simple and sensitive synchronous fluorimetric, and second derivative synchronous fluorometric methods were developed for the validated and simultaneous determination of sulpiride (SLP) and its alkaline degradation product (DSLP). The method is based on measuring the synchronous fluorescence of both the drug and its degradation product in borate buffer of pH 8 at Δ λ of 45 nm. The peak amplitude ( 2D) was measured at 295.5 and 342 nm for SLP and DSLP, respectively. The different experimental parameters affecting the synchronous fluorescence intensity of both compounds were studied and optimized. The fluorescence–concentration plots were rectilinear over the range of 0.05–1.0 and 2–10 μg mL −1 for SLP and DSLP, respectively. The limits of detection (LOD) were 0.02 and 0.4 μg mL −1 and quantification limits (LOQs) were 0.05 and 1.2 μg mL −1 for SLP and DSLP, respectively. The proposed methods were successfully applied to commercial capsules and tablets. Statistical comparison of the results with those of the official method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods, respectively. The method was utilized to study the kinetics of the alkaline induced degradation of the drug. The application was further extended to include the in vivo and in vitro determination of sulpiride. The mean % recoveries ( n = 3) were 100.22 ± 2.04 and 92.00 ± 3.00 for spiked and real human plasma, respectively.

Stability-indicating methods for the determination of sertaconazole nitrate by micelle-enhanced spectrofluorimetry and TLC-densitometry

Two sensitive and selective stability-indicating methods were developed for the determination of sertaconazole nitrate (Ser-NO3), in the presence of its acid, alkaline and oxidative degradation products. The first method was based on measuring the fluorescence intensity of the drug at λex/λem = 231 nm/312 nm. The influence of micelle medium on the fluorescence emission was studied. The nonionic surfactant of Triton® X-100 showedstrong sensitizing effect for the fluorescence. The fluorescence intensity plot was linear over concentrations 0.5–5 μg mL-1 with mean percentage recoveries 100.59 ± 1.49 %. The second method was based on TLC separation of the drug from its degradation products followed by densitometric measurement of the intact drug spot at 302 nm. The developing system used for separation was chloroform-acetone-33 % ammonia (14:2:0.1 v/v/v). The linear range was 1–8 μg/spot with mean percentage recoveries 100.07 ± 1.97 %. The methods were validated according to ICH guidelines. Statistical analysis of the results revealed high accuracy and good precision. The suggested procedures could be used for the determination of sertaconazole nitrate in drug substance and drug products as well as in presence of its degradation products.

Study of active naphtodianthrone St John's Wort compounds by electrospray ionization Fourier transform ion cyclotron resonance and multi‐stage mass spectrometry in sustained off‐resonance irradiation collision‐induced dissociation and infrared multiphoton dissociation modes

Five well-known active naphtodianthrone constituents of Hypericum perforatum (St John's Wort) extracts have been investigated by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) and ESI-FTICRMSn. The studied compounds were hypericin, pseudohypericin, protohypericin, protopseudohypericin (biosynthetic precursors of the two former compounds, respectively) and isopseudohypericin (alkaline degradation product of pseudohypericin). Dissociation mass spectrometry measurements performed on the [M-H]- ion presented a variable efficiency as a function of the used activation mode. Sustained off-resonance irradiation collision-induced dissociation (SORI-CID) only led to a restricted number of fragment ions. In contrast, IRMPD ensured the detection of numerous product ions. Ions detected in ESI-FTICRMS and ESI-FTICRMSn experiments were measured with a very high mass accuracy (typically mass error is lower than 0.5 mDa at m/z close to 500) that allowed unambiguous formulae to be assigned to each signal observed in a mass spectrum. In spite of similar structures, specific fragmentation patterns were observed for the different compounds investigated. This study may be useful in the future to characterize in natural extracts these compounds (or derivatives of these compounds) by liquid chromatography/tandem mass spectrometry (LC/MS/MS) experiments by considering the MS/MS transitions highlighted in this paper.

Quantitative mass spectrometric analysis of ropivacaine and bupivacaine in authentic, pharmaceutical and spiked human plasma without chromatographic separation.

The present study employs time of flight mass and bupivacaine in authentic, pharmaceutical and spiked human plasma as well as in the presence of their impurities 2,6-dimethylaniline and alkaline degradation product. The method is based on time of flight electron spray ionization mass spectrometry technique without preliminary chromatographic separation and makes use of bupivacaine as internal standard for ropivacaine, which is used as internal standard for bupivacaine. A linear relationship between drug concentrations and the peak intensity ratio of ions of the analyzed substances is established. The method is linear from 23.8 to 2380.0 ng mL(-1) for both drugs. The correlation coefficient was >or=0.996 in authentic and spiked human plasma. The average percentage recoveries in the ranges of 95.39%-102.75% was obtained. The method is accurate (% RE < 5%) and reproducible with intra- and inter-assay precision (RSD% < 8.0%). The quantification limit is 23.8 ng mL(-1) for both drugs. The method is not only highly sensitive and selective, but also simple and effective for determination or identification of both drugs in authentic and biological fluids. The method can be applied in purity testing, quality control and stability monitoring for the studied drugs.

Flow field-flow fractionation/multiangle light scattering of sodium hyaluronate from various degradation processes

Sodium hyaluronate (NaHA) is an ultrahigh molecular weight polysaccharide that is found in body tissues, synovial fluid, the vitreous humor, and the umbilical cord, and the size characterization of NaHA is important in pharmaceutical applications. On-line field-flow fractionation/multiangle light scattering/differential refractive index (FlFFF/MALS/DRI) has been applied for the study of degradation efficiency of sodium hyaluronate (NaHA). A NaHA raw sample was degraded by different chemical or physical methods and the degraded NaHA samples were separated using field-programming FlFFF, in which separation is achieved by differences in diffusion coefficients or hydrodynamic diameters. Separation was followed by serial detection using MALS and DRI. Molecular weight distribution (MWD) and information relating to the radius of gyration of the NaHA samples were examined for the raw and degraded NaHA samples. Samples studied include: two different products of ultrasonic degradation, two products of alkaline degradation, and four different products of enzymatic degradation. While alkaline degradation showed a moderate degradation compared to ultrasonic and enzymatic methods in reducing average MW, the latter two degradation methods showed significant changes in average molecular weight and in conformation of NaHA.

Isolation and characterization of process related impurities and degradation products of bicalutamide and development of RP-HPLC method for impurity profile study

A reversed-phase high-performance liquid chromatographic method was developed for determination of process impurities and degradation products of bicalutamide in bulk drug and pharmaceutical formulations. The separation was accomplished on a Symmetry C 18 (4.6 mm × 250 mm; particle size 5 μm) column under isocratic mode. The mobile phase was 0.01 M KH 2PO 4 (pH 3.0):acetonitrile (50:50 v/v) and a PDA detector set at 215 nm was used for detection. Forced degradation of bicalutamide was carried out under thermal, photo, acidic, alkaline and peroxide conditions. The unknown process impurities and alkaline degradation products were isolated and characterized by ESI-MS/MS, 1H NMR and FT-IR spectral data. Under alkaline conditions bicalutamide was degraded in to an acid and an amine. The kinetics of degradation was studied. The proposed method was validated and successfully applied to the analysis of commercial formulations. Thus, the developed method can be used for process development as well as quality assurance of bicalutamide in bulk drug and pharmaceutical formulations.

Validated stability-indicating methods for determination of cilostazol in the presence of its degradation products according to the ICH guidelines

Sensitive and selective stability-indicating assay methods (SIAMs) are suggested for the determination of cilostazol (CIL) in the presence of its acid, alkaline and oxidative degradation products. Developing SIAMs is necessary to carry out any stability study. Stress testing of CIL was performed according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing showed that CIL underwent acid, alkaline and oxidative degradation; on the other hand, it showed stability towards photo- and thermal degradation. Two chromatographic SIAMs were developed, namely HPLC and HPTLC methods. The concentration range and the mean percentage recovery were 1.0–31.0 μg/ml and 99.96 ± 0.46 and 0.6–14.0 μg/spot and 99.88 ± 1.10 for HPLC and HPTLC methods, respectively. In addition, derivative spectrophotometric methods were developed in order to determine CIL in the presence of its acid degradation product; these were performed by using the third derivative spectra ( 3D) and the first derivative of the ratio spectra ( 1DD) methods. The linearity range and the mean percentage recovery were 2.0–34.0 μg/ml and 100.27 ± 1.20 for the ( 3D) method, while they were 2.0–30.0 μg/ml and 99.94 ± 1.18 for the ( 1DD) method. Also, two chemometric-assisted spectrophotometric methods, based on using partial least squares (PLS) and concentration residual augmented classical least squares method (CRACLS), for the determination of CIL were developed. Both methods were applied on zero order spectra of the mixtures of CIL and its acid degradation product, the mean percentage recovery was 100.03 ± 1.09 and 99.91 ± 1.27 for PLS and CRACLS, respectively. All methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied on bulk powder and pharmaceutical formulations.

Determination of tsumacide residues in vegetable samples using a flow‐injection chemiluminescence method

A sensitive, simple and rapid flow-injection chemiluminescence (FI-CL) method is described to determine tsumacide pesticide residue based on the CL reaction of the alkaline degradation product of tsumacide with acidic KMnO(4) when rhodamine 6G was present. Under the optimum conditions, the relative CL intensity is linear with the concentration of tsumacide in the range of 2.0 x 10(-3)-0.20 mg/L. The detection limit is 6.6 x 10(-4) mg/L (3sigma) and the relative standard deviation for 2.0 x 10(-2) mg/L tsumacide solution was 2.28% (intra-day) and 4.85% (inter-day). The proposed method has been applied to determine the residue of tsumacide in vegetable samples and the recovery test is very satisfactory.

Application of spectrophotometric, densitometric, and HPLC techniques as stability indicating methods for determination of Zaleplon in pharmaceutical preparations

Spectrophotometric, spectrodensitometric and HPLC are stability indicating methods described for determination of Zaleplon in pure and dosage forms. As Zaleplon is easily degradable, the proposed techniques in this manuscript are adopted for its determination in presence of its alkaline degradation product, namely N-[4-(3-cyano-pyrazolo[1,5a]pyridin-7-yl)-phenyl]- N-ethyl-acetamide. These approaches are successfully applied to quantify Zaleplon using the information included in the absorption spectra of appropriate solutions. The second derivative (D 2) spectrophotometric method, allows determination of Zaleplon without interference of its degradate at 235.2 nm using 0.01N HCl as a solvent with obedience to Beer's law over a concentration range of 1–10 μg ml −1 with mean percentage recovery 100.24 ± 0.86%. The first derivative of the ratio spectra ( 1DD) based on the simultaneous use of ( 1DD) and measurement at 241.8 nm using the same solvent and over the same concentration range as (D 2) spectrophotometric method, with mean percentage recovery 99.9 ± 1.07%. The spectrodensitometric analysis allows the separation and quantitation of Zaleplon from its degradate on silica gel plates using chloroform:acetone:ammonia solution (9:1:0.2 by volume) as a mobile phase. This method depends on quantitave densitometric evaluation of thin layer chromatogram of Zaleplon at 338 nm over a concentration range of 0.2–1 μg band −1, with mean percentage recovery 99.73 ± 1.35. Also a reversed-phase liquid chromatographic method using 5-C8 (22 cm × 4.6 mm i.d. 5 μm particle size) column was described and validated for quantitation of Zaleplon using acetonitrile:deionised water (35:65, v/v) as a mobile phase using Paracetamol as internal standard and a flow rate of 1.5 ml min −1 with UV detection of the effluent at 232 nm at ambient temperature over a concentration range of 2–20 μg ml −1 with mean percentage recovery 100.19 ± 1.15%. The insignificance difference of the proposed methods results with those of the reference one proved their accuracy and precision.

Quantitative determination of the main aliphatic carboxylic acids in wood kraft black liquors by high-performance liquid chromatography–mass spectrometry

The versatile characterization of organic material and especially of the significant aliphatic hydroxy acids in black liquor is of great importance, for example, in monitoring the progress of the kraft pulping process. This paper describes a simple high-performance liquid chromatographic separation method with atmospheric-pressure chemical ionization mass spectrometry (HPLC–APCI-MS) which was developed for the rapid quantitative analysis of these acids, mainly formed as the alkaline degradation products of feedstock carbohydrates. The fraction of carbohydrate degradation products is mainly composed of hydroxy monocarboxylic and volatile acids (formic and acetic acids) along with lesser amounts of various dicarboxylic acids. This method was thoroughly tested and validated to determine the most abundant nonvolatile low-molecular-mass aliphatic mono- and dicarboxylic acids present in softwood (pine and spruce) and hardwood (birch and aspen) kraft black liquors. This straightforward technique provides, compared to the conventional gas chromatographic methods, some important advantages such as simple sample preparation and a faster analysis time, thus enabling almost real-time monitoring of these acids.

A fast method for determining low‐molecular‐mass aliphatic carboxylic acids by high‐performance liquid chromatography–atmospheric pressure chemical ionization mass spectrometry

A fast quantitative high-performance liquid chromatographic separation method with atmospheric pressure chemical ionization mass spectrometric detection (HPLC-APCI-MS) was developed for the determination of low-molecular-mass aliphatic mono- and dicarboxylic acids typically present in different industrial process waters. A mixture of glycolic, lactic, a-glucoisosaccharinic, oxalic, maleic, fumaric, succinic, malic, glutaric, methylsuccinic, and adipic acids was separated using an RP chromatographic system. Adipic acid was used as an internal standard to calculate correlation coefficients for the acids studied. The chromatographic analysis of these acids was primarily carried out by means of gradient elution with an aqueous formic acid solution (0.15%, pH 2.5) and methanol using a modified C18 stationary phase. Good acid separation could be obtained for all acids by optimizing the chromatographic conditions. The method provides a simple sample preparation and faster analysis time compared to the traditional gas chromatographic methods, thus enabling almost real-time monitoring of these acids. Finally, the method developed was applied to the analysis of a complex mixture of aliphatic hydroxy carboxylic acids, which are formed as alkaline degradation products of carbohydrates during wood delignification and are present in the cooking spent liquor (black liquor).

Xylo‐Oligosaccharide (XOS) Formation through Hydrothermolysis of Xylan Derived from Viscose Process

AbstractXylo‐oligosaccharides (XOS) have gained growing interest during the past decade owing to their beneficial influence on health. At the same time, a trend to a more effective utilization of biomass and biomass degradation products can be observed. As a consequence, also the steeping‐lye of the viscose process is discussed as a potential source of new products based on xylans, xylooligosaccharides, xylose, and different xylose degradation products, thus being a driving force for the development of appropriate production processes. Therefore, xylan isolated from the steeping‐lye was subjected to hydrothermal degradation for production of xylo‐oligosaccharides (XOS). The experiments were carried out at 120, 150, and 180 °C, respectively. This hydrothermal treatment led to a soluble fraction, consisting of neutral and acidic XOS, and an insoluble residue predominantly made up of highly crystalline cellulose. A mass balance was established to calculate the activation energy for hydrothermal xylan degradation from weight loss kinetics. The degree of polymerization (DP) of the neutral product fraction could be influenced in a wide range by the reaction conditions applied. Acidic XOS were further characterized using mass spectrometry (MS). A 4‐O‐methylglucuronic acid residue α‐(1,3)‐linked to the xylose backbone was detected as a new structural element in alkaline degradation products derived from beech wood xylan.

New insights into wood and cement interaction

AbstractThis work deals with the influence of poplar extractives and poplar alkaline degradation products on the hydration of cement. The wood chemical composition was characterized to determine the impact of soft alkaline conditions on wood fiber. Some of the constituents were hydrolyzed and converted into carboxylic acids, which were identified and quantified. Monitoring by electrical conductivity clearly showed that wood extractives are less effective than wood alkaline degradation products in inhibiting the hydration of cement.

Liquid chromatography and chemometric methods for determination of rofecoxib in presence of its photodegradate and alkaline degradation products

Rofecoxib (I) has been determined in presence of its photodegradate (II) and alkaline degradation products (III) and (IV) by liquid chromatography method using a Shimpak ODS C18 column (150mm × 4.5mm i.d.) and acetonitrile/0.05% phosphoric acid (35:65) at pH 2.6. The method could determine (I) in the range of 0.3–28μgml−1 with mean percentage recovery of 100.29 ± 0.979%. Also, two chemometric methods were developed using partial least square (PLS) and concentration residual augmented classical least square method (CRACLS). The methods could determine (I) in presence of (II), (III) and (IV) with linearity range of 2–36μgml−1 and with mean percentage recovery of 99.53 ± 1.613 and 99.31 ± 1.42% for PLS and CRACLS, respectively. The PLS method was used to carry out a kinetic study of the alkaline degradation. The reaction rate constant was found to be k = 0.051min−1 and the t1/2 =13.5min using 0.051M sodium hydroxide at 25°C, other kinetic data were also presented. The three methods were applied to the analysis of pharmaceutical dosage forms and bulk powder.

Study of coloured components formed in sugar beet processing

The main characteristics of the most troublesome colourants formed throughout sugar beet manufacture are summarised. A review of the reaction mechanisms, structures and factors affecting their formation is presented to enhance understanding of the nature of coloured impurities and to propose effective measures for controlling their formation through the process. The main colourants formed in sugar beet processing were synthesised, analysed by gel permeation chromatography (GPC) and characterised by their molecular weights and UV–Vis spectra. The GPC analysis of a sugar beet thin juice showed the presence of coloured compounds with molecular weights ranging from 0.4 to >100 kDa. Spectral analysis confirmed the presence of melanoidins and alkaline degradation products of hexoses in the juice. There is a substantial increase in colour after the evaporation step. Therefore, the coloured impurities of thin juices have to be removed before subsequent stages to produce white sugar of high quality.

Ratio Derivative S~ectrophotometricM ethod for the Determination of Some Oxicams in Presence of their Alkaline Dearadation Products

A new spectrophotometric method has been developed for the determination of some oxicams namely, lornoxicam (LX) , tenoxicam (TX) and meloxicam (MX), in the presence of their main alkaline degradation products, 2-aminopyridine ( I ) and 2-amino-5-methylthiazole (II) for (TX&amp;MX), 2-aminopyridine and TX for lornoxicam. The method is based on the use of the first derivative of the ratio spectra (1DD) of the mentioned compounds and their corresponding degradates. The procedure does not require any separation steps. Linear calibration graphs of 1DD were obtained by measurement of the amplitudes at 316, 249 and 260nm for LX, 248.8 , 258.8 nm for TX and 287.2nm for MX. On carrying out measurements at the above mentioned wavelengths, the linearity range is found to be 2.5 - 35 μg ml-1 for LX and TX, 1.25 - 30 μg ml-1 for MX. The validity of the method was assessed by applying the standard addition technique. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The suggested procedure could be used for the determination of the above mentioned drugs in pure and dosage forms as well as in presence of their degradation products.

Stability-indicating methods for the determination of linezolid in the presence of its alkaline-induced degradation products

Three methods are presented for the determination of linezolid in the presence of its alkaline-induced degradation products. The first method was based on separation of linezolid from its alkaline degradation product by TLC followed by densitometric measurement of the spots of intact drug at 244 nm. The separation was carried out on silica gel 60 F 254 using isobutanol:ammonia (9:1 v/v) as a mobile phase. The second method was based on first derivative 1D ultraviolet spectrophotometry with zero crossing point and peak to base measurement. The 1D value at 251.4 nm was selected for the assay of linezolid in the presence of degradation product. The third method was depended on the first derivative of the ratio spectra 1DD by measurement of the value at 263.6 nm. The proposed methods were successfully applied to the determination of the drug in bulk powder, in laboratory prepared mixtures with its degradation product and in commercial tablets.

Effects of Technical Adsorbents and Cleaning Agents in a Cement Matrix – A Case Study

ABSTRACTThe effects of organic cleaning agents (totally three) and degradation products from solid technical adsorbents (two) on the sorption of Eu on cement and TiO2 were measured with variation of concentration (0.001–10 % of the water phase for the cleaning agents, alkaline degradation products corresponding to 0.03–8 mM DOC for the adsorbents) and reaction time (up to 420 d). The effects of the cleaning agents Industrikombi and Prefect Citron were minor. The degradation of the ion exchanger (metaacrylic polymer) had no significant effect on the Eu-sorption. The other adsorbent (filter aid, inert fibre; acrylonitrile polymer) was rapidly degrading at high pH, and the degradation products had a significant reducing effect on the sorption of Eu at added DOC-levels in the mM-range. This category of adsorbent materials should not be incorporated in a cement waste matrix or be stored in a cementitious environment together with radionuclides.

Elucidation of the structure of the lipopolysaccharide core and the linkage between the core and the O-antigen in Pseudomonas aeruginosa immunotype 5 using strong alkaline degradation of the lipopolysaccharide.

The products of the strong alkaline degradation of the lipopolysaccharide (LPS) of Pseudomonas aeruginosa immunotype 5 were separated by anion-exchange HPLC and studied by electrospray ionization mass spectrometry and NMR spectroscopy. It was found that two major products have the same inner core region and lipid A carbohydrate backbone (A) but different outer core regions (B and C). The difference is in the position of a rhamnose residue, which is substituted with either an additional glucose residue (B) or a disaccharide remainder of the degraded O-polysaccharide (C). The site and the configuration of the linkage between the O-polysaccharide and the core were determined and, together with published data, the structure of the so-called biological repeating unit of the O-antigen was defined (D). The glycosidic linkage of the quinovosamine residue is beta when it links the O-polysaccharide to the core (C) and alpha when it connects the interior repeating units of the O-polysaccharide to each other (D) [Formula: see text]. In the structures shown Rha stands for rhamnose, Kdo for 3-deoxy-D-manno-oct-2-ulosonic acid, Hep for L-glycero-D-manno-heptose, GalNAcA for 2-acetamido-2-deoxygalacturonic acid, QuiN for 2-amino-2,6-dideoxyglucose (quinovosamine), DeltaHexNA for 2-amino-2-deoxy-D-threo-hex-4-enuronic acid; all monosaccharides are in the pyranose form and have the D configuration, except for Rha and GalNAcA that have the L configuration. In C, the remainder of the degraded O-polysaccharide is shown in bold type.

Degradation of cellulose under alkaline conditions

A review of the important area of cellulose degradation under alkaline conditions is presented; it focuses on its relevance to the possible disposal of radioactive wastes in an underground repository in which cement-based waste encapsulation grouts and backfill may be employed. An overview of the alkaline degradation pathways of monosaccharides and substituted monosaccharides is initially presented, before progressing to the reactions involved in the alkaline degradation of cellulose, namely end-wise degradation, termination, alkaline scission, and oxidative alkaline degradation. Physical factors affecting reaction rates and the alkaline degradation of hemicellulose are also discussed. A review of the identity of the commonly detected alkaline degradation products (and their numerous synonyms) is presented, along with discussion of the rates of degradation of cellulose.