Radiation effect studies on anticancer drugs, cyclophosphamide and doxorubicin for radiation sterilization

Two anticancer drugs, cyclophosphamide (CPH) and doxorubicin hydrochloride (DOXO), in powder form were exposed to a range of doses of ⁶⁰Co gamma and electron beam radiation to study the effects of ionizing radiation. Pharmacopoeia tests, discolouration, degradation products, effect of irradiation temperature and dose rate were investigated. CPH undergoes less than 2% degradation at 30 kGy. Chromatographic studies revealed formation of several trace level degradation products, discolouration and free radicals in the irradiated CPH. N,N-bis (2-chloroethyl) group in the molecule is particularly sensitive to radiation degradation. Irradiation to 5 kGy at low temperature (77 K) did not result in significant changes. DOXO was observed to be quite radiation resistant and did not undergo significant changes in its physico-chemical properties and degradation product profile. It can be radiation sterilized at normal sterilization dose of 25 kGy.     

Spectrophotometric stability-indicating methods for the determination of leflunomide in the presence of its degradates

Five simple and sensitive methods were developed for the determination of leflunomide (I) in the presence of its degradates 4-trifluoromethyl aniline (II) and 3-methyl-4-carboxy isoxazole (III). Method A was based on differential derivative spectrophotometry by measuring the delta(1)D value at 279.5 nm. Beer's law was obeyed in the concentration range of 2.00-20.00 microg/mL with mean percentage accuracy of 100.07 +/- 1.32. Method B depended on first-derivative spectrophotometry and measuring the amplitude at 253.4 nm. Beer's law was obeyed in the concentration range of 2.00-16.00 microg/mL with mean percentage accuracy of 98.42 +/- 1.61. Method C was based on the reaction of degradate (II) with 2,6-dichloroquinone-4-chloroimide (Gibbs reagent). The colored product was measured at 469 nm. Method D depended on the reaction of degradate (II) with para-dimethyl aminocinnamaldehyde (p-DAC). The absorbance of the colored product was measured at 533.4 nm. Method E utilized 3-methyl-2-benzothiazolinone hydrazone in the presence of cerric ammonium sulfate with degradate (II). The green colored product was measured at 605.5 nm. The linearity range was 40.00-280.00, 2.40-24.00, and 30-250 microg/mL with mean percentage accuracy of 100.75 +/- 1.21, 100.13 +/- 1.45, and 99.74 +/- 1.39 for Methods C-E, respectively. All variables were studied to optimize the reaction conditions. The proposed methods have been successfully applied to the analysis of leflunomide in pharmaceutical dosage forms and the results were statistically compared with that previously reported.     

Flow-injection-enhanced chemiluminescence method for the determination of four anticancer drugs

Novel chemiluminescence (CL) reaction systems were established for the determination of anticancer drugs, including adriamycin (ADM), hydroxycamptothecin (HCPT), mitomycin (MMC), and fluorouracil (5-FU). The formaldehyde-sensitized CL emission mechanism was developed for four systems by comparing the fluorescence emission and CL spectra. For ADM-KMnO₄-HNO₃, HCPT-KMnO₄-H₂SO₄, MMC-KMnO₄-HNO₃, and 5-FU-KMnO₄-HCl systems, the illuminant was a singlet state bimolecule oxygen, ¹O₂ ¹O₂(¹Δ_g ¹Δ_g), which was formed from ¹O₂ (¹Δ_g) produced in the reaction system. The illuminant emits CL spectra at 539 or 549 nm. The presence of formaldehyde can sensitize CL emission because it may accelerate the generation of ¹O₂ (¹Δ_g). The optimum conditions for the CL emission were chosen. The relationships between the relative CL intensity and the concentration of the studied analytes are linear with the correlation coefficients in the range of 0.9959–0.9989. The proposed four enhanced CL systems provide a good linearity, a high sensitivity, precision, and the potential capability for the determination of anticancer drugs in biological samples. The text was submitted by the authors in English.     

Polymer membrane sensors for sildenafil citrate (Viagra) determination in pharmaceutical preparations

The construction and performance characteristics of ion selective membrane electrodes for sildenafil citrate (SC) drug (the active component of Viagra) are described. The proposed sensors are based on the formation of the complex ion associates of SC with sodium tetraphenylborate (SC-TPB) and phosphomolybdic acid (SC-PMA) as ionophores in poly vinyl chloride membrane (PVC). Both electrodes SC-PMA and SC-TPB showed a linear and stable potential response with near-Nernstian slope of 55.5±0.35 and 53.5±0.3 mV per decade over a wide range of concentration 10⁻² to 10⁻⁵ M sildenafil with good reproducibility, respectively. The electrodes showed a fast response time of 30 and 40 s. and were used over a wide range of pH 3-6. The selectivity coefficients indicated good selectivity for SC drug over a large number of nitrogenous compounds and some inorganic cations. The proposed sensors are tested for the analysis of SC in pure form, pharmaceutical preparations and blood serum. An average recovery of 98.9-99.5±0.6% and correlation to the existing methods of 0.998 were achieved.     

Sensitive and rapid spectrophotometric methods for determination of anticancer drugs

Sensitive, rapid, and simple spectrophotometric methods were developed for determination of the anticancer drugs vinblastine sulfate (VBS) and vincristine sulfate (VCS), which belong to the class of vinca alkaloids. The first method is based on the reaction of VBS and VCS with diazotized dapsone, forming yellow azo products with absorption maxima at 430 nm. The colored species obey Beer's law in the concentration range of 0.5-24 microg/mL for VBS and 0.5-12 microg/mL for VCS. The second method describes the reaction of VBS and VCS with iron(III) and subsequent reaction with ferricyanide in hydrochloric acid medium to yield blue products with absorption maxima at 750 nm. The Beer's law range for this method is 0.1-4 microg/mL for VBS and 0.5-10 microg/mL for VCS. With both methods, colored species were stable for 1 h. The methods are simple and reproducible and are applied for determination of VBS and VCS in pharmaceutical formulations. Commonly encountered pharmaceuticals added as excipients do not interfere in the analysis and the results obtained in the analysis of dosage forms agree well with the labeled contents.     

HPLC, TLC, and first-derivative spectrophotometry stability-indicating methods for the determination of tropisetron in the presence of its acid degradates

Three stability-indicating assay methods were developed for the determination of tropisetron in a pharmaceutical dosage form in the presence of its degradation products. The proposed techniques are HPLC, TLC, and first-derivative spectrophotometry (1D). Acid degradation was carried out, and the degradation products were separated by TLC and identified by IR, NMR, and MS techniques. The HPLC method was based on determination of tropisetron in the presence of its acid-induced degradation product on an RP Nucleosil C18 column using methanol-water-acetonitrile-trimethylamine (65 + 20 + 15 + 0.2, v/v/v/v) mobile phase and UV detection at 285 nm. The TLC method was based on the separation of tropisetron and its acid-induced degradation products, followed by densitometric measurement of the intact spot at 285 nm. The separation was carried out on silica gel 60 F254 aluminum sheets using methanol-glacial acetic acid (22 + 3, v/v) mobile phase. The 1D method was based on the measurement of first-derivative amplitudes of tropisetron in H2O at the zero-crossing point of its acid-induced degradation product at 271.9 nm. Linearity, accuracy, and precision were found to be acceptable over concentration ranges of 40-240 microg/mL, 1-10 microg/spot, and 6-36 micro/mL for the HPLC, TLC, and 1D methods, respectively. The suggested methods were successfully applied for the determination of the drug in bulk powder, laboratory-prepared mixtures, and a commercial sample.     

Recent advances in electrochemical sensors for antibiotics and their applications

The abuse of antibiotics will cause an increase of drug-resistant strains and environmental pollution,which in turn will affect human health.Therefore,it is important to develop effective detection techniques to determine the level of antibiotics contamination in various fields.Compared with traditional detection methods,electrochemical sensors have received extensive attention due to their advantages such as high sensitivity,low detection limit,and good selectivity.In this mini review,we summarized the latest developments and new trends in electrochemical sensors for antibiotics.Here,modification methods and materials of electrode are discussed.We also pay more attention to the practical applications of antibiotics electrochemical sensors in different fields.In addition,the existing problems and the future challenges ahead have been proposed.We hope that this review can provide new ideas for the development of electrochemical sensors for antibiotics in the future.     

Room-temperature phosphorimetry for the determination of trace contaminations of camptothecin in anticancer drugs

Campthotecin derivatives, irinotecan (CPT-11) and topotecan (TPT), have been used for the treatment of cancer and camptothecin (CPT) is a potential contaminant in these anticancer medicines. In this work, room-temperature phosphorimetry was used to quantify either CPT as trace contaminants in anticancer drugs and CPT-11 as the main ingredient in anticancer medicines. Phosphorescence from CPT-11 was induced using Pb(NO₃)₂ in SDS treated cellulose substrate while CPT was selectively detected using TlNO₃ as a phosphorescence enhancer in either cellulose or nylon substrates. The limit of quantification for CPT and CPT-11 was in ng order. A detailed metrological study was made to calculate the combined uncertainty associated to the CPT phosphorescence measurement. Satisfactory analyte recoveries were obtained for CPT-11 as a main active ingredient of a pharmaceutical formulation. The selective determination of CPT in a matrix containing TPT was made using the higher order (2nd) derivative of the excitation spectra. The results demonstrated the applicability of the method due its simplicity, cost effectiveness and selectivity.     

Calibration method for determination of acids and bases with piezoelectric quartz crystal sensors

Based on the linear relation between the frequency response of the piezoelectric quartz crystal sensor and the conductivity of the solution to be measured, calibration models for quantitative analysis of acid and base systems are derived and are verified both theoretically and experimentally. Then quantitative determinations of aspirin and penicilline were done with the calibration technique. The quantitative analysis results of the two true pharmaceutical systems indicate that the models, combining linear regression, can give precise and accurate concentration estimates, which can reduce the influence of the presence of interferences.     

Utility of oxidation-reduction reaction for the determination of ranitidine hydrochloride in pure form,in dosage forms and in the presence of its oxidative degradates

Three simple, accurate and sensitive colorimetric methods (A, B and C) for the determination of ranitidine HCl (RHCl) in bulk sample, in dosage forms and in the presence of its oxidative degradates are described. The first method A is based on the oxidation of the drug by N-bromosuccinimide (NBS) and determination of the unreacted NBS by measurement of the decrease in absorbance of amaranth dye (AM) at a suitable lambda(max)=520 nm. The methods B and C involve the addition of excess Ce(4+) and determination of the unreacted oxidant by decrease the red color of chromotrope 2R (C2R) at a suitable lambda(max)=528 nm for method B or decrease the orange pink color of rhodamine 6G (Rh6G) at a suitable lambda(max)=526 nm for method C. Regression analysis of Beer-Lambert plots showed good correlation in the concentration ranges 0.2-3.6, 0.1-2.8 and 0.1-2.6 microg ml(-1) for methods A, B and C, respectively. The apparent molar absorptivity. Sandell sensitivity, detection and quantitation limits were calculated. For more accurate results, Ringbom optimum concentration ranges were 0.3-3.4, 0.2-2.6 and 0.2-2.4 microg ml(-1) for methods A, B and C, respectively. Analyzing pure and dosage forms containing RHCl tested the validity of the proposed methods. The relative standard deviations were 相似文献   

Piezoelectric quartz crystal sensors based on ion-pair complexes for the determination of cinchonine in human serum and urine

A new sensing method for the determination of cinchonine was presented, based on the sensitive mass response of PQC and the selective adsorption of cinchonine on PVC membrane containing ion-pair complex. The proposed sensors show much wider working range (pH range), much higher sensitivity and selectivity than those potentiometric and spectrophotometric methods. In this paper, three counter ions were compared and six complexes synthesized. For the sensor modified with cinchonine-monotetraphenylborate-PVC membrane, calibration graph was linear over concentration range of 5×10⁻⁸-2.1×10⁻⁴ M with a detection limit of 4×10⁻⁸ M at pH 7.1, and recoveries 97.7-108.6%. Influencing factors were investigated in detail and optimized. Results from real samples were satisfactory.     

Electrospray ionization mass spectrometry for analysis of low-molecular-weight anticancer drugs and their analogues

In this study, several anticancer drugs and their analogues consisting of organic and organometallic compounds were analyzed by electrospray ionization mass spectrometry (ESI/MS) using a quadrupole mass spectrometer. Protonated molecular ions [M+H]⁺ were observed for all of the compounds studied, and in the case of the two steroid sulfates, deprotonated molecular ions [M-H]^? were obtained. Tandem mass spectrometry was performed on these quasimolecular ions, and the product ions formed provided useful fragmentation patterns that were characteristic for the compounds. This study provides evidence that ESI/MS is a sensitive technique for structure confirmation and identification of small organic and organometallic molecules.     

Coated wire linear alkylbenzenesulfonate sensor based on polypyrrole and improvement of the selectivity behavior

The potentiometric behavior of coated wire electrodes based on dodecylbenzenesulfonate-doped polypyrrole (PPy-DBS) and hyamine as ion exchanger was investigated. The PPy-DBS was prepared electrochemically by anodic polymerization of pyrrole in the presence of DBS⁻ ions in aqueous solution and used as ionophore for construction of the sensor. Two types of coated wire electrodes made of PVC-PPy-DBS and PVC-Hyamine-DBS, plasticized with ortho-nitrophenyloctylether (o-NPOE) showed the Nernstian behavior (with respective calibration slopes of about 58 and 60 mV per decade) over the DBS⁻ concentration range of 3.0×10⁻⁶ to 1.1×10⁻³ M and 5.0×10⁻⁶ to 1.3×10⁻³ M, respectively. The influence of membrane composition, type of plasticizer, and pH of test solution on the potentiometric responses of the two electrodes was investigated. The potentiometric response was independent of the pH of test solution in the range 3-10. The response time of electrodes was fast (10 s for both types of electrode), and they can be used for at least 3 months without any significant change in potential. The proposed electrodes revealed very good selectivity for DBS⁻ ion over diverse inorganic and organic anions. The potentiometric selectivity coefficients for the PPy-DBS based electrode revealed a significant improvement as compared to the electrode made by conventional Hyamine-DBS (Hya-DBS) anion exchanger. The proposed electrode was used for determination of DBS⁻ ion in some commercial detergents. The results of the potentiometric determinations were in satisfactory agreement with those obtained by a standard method (two-phase titration).     

A highly sensitive method for the determination of mercury using vapor generation gold wire microextraction and electrothermal atomic absorption spectrometry

The study introduces a new simple and highly sensitive method for headspace solid phase microextraction (HS-SPME) coupled with electrothermal atomic absorption spectrometric determination of mercury. In the proposed method, a gold wire, mounted in the headspace of a sample solution in a sealed bottle, is used for collection of mercury vapor generated by addition of sodium tetrahydroborate. The gold wire is then simply inserted in the sample introduction hole of a graphite furnace of an electrothermal atomic absorption spectrometry instrument. By applying an atomization temperature of 600 °C, mercury is rapidly desorbed from the wire and determined with high sensitivity.     

Synthesis of new chiral fluorescent sensors and their applications in enantioselective discrimination

Five novel sensors (R,R)-3–6 and (S, S)-6 were synthesized and developed for enantioselective recognition of chiral compounds. Sensor 6 with two thiourea groups and steric π-conjugation frameworks could discriminate different chiral substrates, including acidic compounds, basic compounds, and neutral compounds. These results disclosed that the outstanding performance of enantioselective discrimination could be attributed to the thiourea group which acted as a hydrogen-bonding donor and the bulky steric moiety of the hosts which provided appropriate chiral environment. This result will be of great practical value in the designation of chiral sensors and high-throughput assay of chiral products.     

Synthesis of new chiral fluorescent sensors and their applications in enantioselective discrimination

New chiral fluorescent sensors derived from tetraphenylethylene and proline hydrazide were synthesized and applied in the chiral recognition of various chiral compounds, including unprotected amino acids, acidic compounds, chiral amines and even neutral alcohols. These results demonstrated that the excellent enantioselective response ability to various chiral substrates could be attributed to the –NH moieties of pyrrolidine ring and thiourea unit which acted as hydrogen-bonding donors. This result is of potential significance in enantiomeric discrimination and high-throughput analysis of the enantiomeric purity of chiral guests.     

Ion-selective electrode for the determination of prenalterol

A new prenalterol (Pr) ion-selective PVC membrane electrode based on the ion-pair complex of Pr with sodium tetraphenylborate was prepared and its performance characteristics were studied. The electrode exhibited a linear response with a good Nernstian slope over a relatively wide range of concentration. The electrode whose membrane was made of 8.0% (w/w) of ion pair, 49.5% (w/w) of dioctyl phthalate (DOP) and 43.5% (w/w) of PVC showed characteristics higher than those obtained with the other ones, namely, slope of 56.3 mV per concentration decade, at 25 °C; usable concentration range 1.2×10⁻⁵–3.2×10⁻² M prenalterol; response time ≤20 s. Up to 24 h continuous soaking, the calibration graph slope was constant at 56.0 mV per concentration decade, at 25 °C, then it decreased gradually as the time of soaking increases reaching 41 mV per decade after 11 days. The changes in pH did not affect the electrode performance within the range 2.2–7.5. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. The electrode showed very good selectivity for Pr with respect to a large number of inorganic and organic cations. The standard addition method and potentiometric titration were used to determine Pr in pure solutions and in pharmaceutical formulations. The relative standard deviations (R.S.D.) of the three methods used for the determination of prenalterol in pharmaceutical formulations were 0.8, 2.1 and 1.9% of the extrapolation, standard addition and potentiometric methods, respectively.     

Capacitive sensors using electropolymerized o-phenylenediamine film doped with ion-pair complex as selective elements for the determination of pentoxyverine

A capacitive sensing method based on electropolymerized o-phenylenediamine film doped with pentoxyverine ion-pair complex as selective element was successfully developed for the determination of pentoxyverine. Ion-pair complex, pentoxyverine-tetraphenylborate or pentoxyverine-picrolonate, was embedded in electropolymerized o-phenylenediamine film by electropolymerizing technique. The effects of working frequency and test solution pH on the detection of pentoxyverine were investigated in detail and optimized. For the sensor modified with pentoxyverine-tetraphenylborate, calibration curve was linear over the concentration range of 5.0×10⁻⁷ to 1.0×10⁻⁴ M with a detection limit of 1.0×10⁻⁷ M at pH 7. The proposed sensor exhibited high selectivity and sensitivity to pentoxyverine. The results in sample analysis confirmed the usefulness of the proposed ISC sensor for quantitative analysis, and also indicated that this method might find applications in the assay of other drugs.     

MOFs传感器在癌症及其生物标志物检测中的应用

癌症是世界上最致命的疾病之一,因此癌细胞的有效捕获和敏感检测对基础研究以及临床诊断和治疗都具有重要意义.基于金属有机骨架(MOFs)的催化活性和固有的发光性能等特点,MOFs已被成功地开发为传感平台实现对癌症及其标志物的检测.综述了基于MOFs的电化学、荧光、电化学发光、比色传感器在癌细胞及核酸、蛋白质等生物标志物检测...     

Gondola-shaped tetra-rhenium metallacycles modified evanescent wave infrared chemical sensors for selective determination of volatile organic compounds

Water-stable and cavity-contained rhenium metallacycles were synthesized, and their ability to selectively interact with volatile organic compounds (VOCs) systematically studied using attenuated total reflection infrared (ATR-IR) spectroscopy. Integrating the unique properties of rhenium metallacycles into optical sensing technologies significantly improves selectivity in detecting aromatic compounds. To explore the interaction of rhenium metallacycles with VOCs, the surface of ATR sensing elements was modified with the synthesized rhenium metallacycles and used to detect VOCs. The results indicate that rhenium metallacycles have crown ether-like recognition sites, which can selectively interact with aromatic compounds, especially those bearing polar functional groups. The IR absorption bands of rhenium metallacycles shift significantly upon adsorption of aromatic VOCs, revealing a strong interaction between the tetra-rhenium metallacycles and guest aromatic compounds. Optimizing the thickness of the metallacycles coated on the surface of the sensing element led to rapid response in detection. The dynamic range of response was generally up to 30 mg/L with detection limits ca. 30 μg/L. Further studies of the effect of interferences indicate that recovery can be higher than 95% for most of the compounds tested. The results on the flow-cell device indicated that the performances were similar to a static detection system but the detection of VOCs can be largely simplified.