Emycin-E purified from Streptomyces sp. RG1011 from Himalayan soil has antibiofilm activity against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is an opportunistic pathogen that causes deadly infections in human as well as animals. The intricate network of virulence factors and biofilms are the major hindrance for the antibiotics in the successful treatment of the infection. The aim of this study is to isolate, identify and characterize natural antimicrobial agent against S. aureus from natural resources. METHODS: Himalayan soils were subjected to primary, secondary and tertiary screening to isolate soil Actinobacteria. Identification and characterization of the isolate was done by various biochemical assays and 16s rDNA sequencing. Partial purification of the potent antimicrobial agent was done by n-butanol from the culture supernatant, TLC and HPLC were performed to purify the active component and subjected to FTIR and ESI-MS analysis. RESULTS: The potent isolate RM-1(13) was confirmed as Streptomyces griseus strain RG1011 (NCBI accession no: 0M780275) by biochemical and molecular analysis. The partially purified antimicrobial agent was active against various Gram-positive and Gram-negative pathogens. The active component was purified by HPLC and identified as Emycin-E by ESI-MS analysis. The Emycin-E has calculated MIC of 0.31 µg/ml against S. aureus ATCC 25923. Emycin-E inhibits the biofilm formation of S. aureus in in vitro microtiter plate assay. CONCLUSIONS: The identified antimicrobial agent was found active against various Gram-positive and Gram-negative pathogens. We have successfully identified the active compound as Emycin-E by FTIR and ESI-MS analysis. Our study suggests the role of Emycin-E in the inhibition of biofilm formation in S. aureus.

Translational Research Symposium-collaborative efforts as driving forces of healthcare innovation.

The 5th Translational Research Symposium was organised at the annual meeting of the European Society for Biomaterials 2018, Maastricht, the Netherlands, with emphasis on the future of emerging and smart technologies for healthcare in Europe. Invited speakers from academia and industry highlighted the vision and expectations of healthcare in Europe beyond 2020 and the perspectives of innovation stakeholders, such as small and medium enterprises, large companies and Universities. The aim of the present article is to summarise and explain the main statements made during the symposium, with particular attention on the need to identify unmet clinical needs and their efficient translation into healthcare solutions through active collaborations between all the participants involved in the value chain.

Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis.

Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance.IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.

The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial.

BACKGROUND: Long-term macrolide treatment has proven benefit in inflammatory airways diseases, but whether it leads to changes in the composition of respiratory microbiota is unknown. We aimed to assess whether long-term, low-dose erythromycin treatment changes the composition of respiratory microbiota in people with non-cystic fibrosis bronchiectasis. METHODS: Microbiota composition was determined by 16S rRNA gene sequencing of sputum samples from participants in the BLESS trial, a 12-month, double-blind, placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg) in adult patients with non-cystic fibrosis bronchiectasis and at least two infective exacerbations in the preceding year. The primary outcome was within-patient change in respiratory microbiota composition (assessed by Bray-Curtis index) between baseline and week 48, comparing erythromycin with placebo. The BLESS trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000460303. FINDINGS: The BLESS trial took place between Oct 15, 2008, and Dec 14, 2011. Paired sputum samples were available from 86 randomly assigned patients, 42 in the placebo group and 44 in the erythromycin group. The change in microbiota composition between baseline and week 48 was significantly greater with erythromycin than with placebo (median Bray-Curtis score 0·52 [IQR 0·14-0·78] vs 0·68 [0·46-0·93]; median difference 0·16, 95% CI 0·01-0·33; p=0·03). In patients with baseline airway infection dominated by Pseudomonas aeruginosa, erythromycin did not change microbiota composition significantly. In those with infection dominated by organisms other than P. aeruginosa, erythromycin caused a significant change in microbiota composition (p=0·03 [by analysis of similarity]), representing a reduced relative abundance of Haemophilus influenzae (35·3% [5·5-91·6] vs 6·7% [0·8-74·8]; median difference 12·6%, 95% CI 0·4-28·3; p=0·04; interaction p=0·02) and an increased relative abundance of P aeruginosa (0·02% [0·00-0·33] vs 0·13% [0·01-39·58]; median difference 6·6%, 95% CI 0·1-37·1; p=0·002; interaction p=0·45). Compared with placebo, erythromycin reduced the rate of pulmonary exacerbations over the 48 weeks of the study in patients with P. aeruginosa-dominated infection (median 1 [IQR 0-3] vs 3 [2-5]; median difference -2, 95% CI -4 to -1; p=0·01), but not in those without P. aeruginosa-dominated infection (1 [0-2] vs 1 [0-3]; median difference 0, -1 to 0; p=0·41; interaction p=0·04). INTERPRETATION: Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis. In patients without P. aeruginosa airway infection, erythromycin did not significantly reduce exacerbations and promoted displacement of H. influenzae by more macrolide-tolerant pathogens including P. aeruginosa. These findings argue for a cautious approach to chronic macrolide use in patients without P. aeruginosa airway infection. FUNDING: Mater Adult Respiratory Research Trust Fund.

Interaction of erythromycin ethylsuccinate and acetaminophen with protein fraction of extracellular polymeric substances (EPS) from various bacterial aggregates.

Extracellular polymeric substances (EPS) are, along with microbial cells, the main components of the biological sludges used in wastewater treatment and natural biofilms. EPS play a major role in removing pollutants from water by means of sorption. The ability of soluble EPS (S-EPS) and bound EPS (B-EPS) derived from various bacterial aggregates (flocs, granules, biofilms) to bind at pH 7.0 ± 0.1 to two pharmaceutical substances, acetaminophen (ACE) and erythromycin ethylsuccinate (ERY), has been investigated using the fluorescence quenching method. Two intense fluorescence peaks, A (Ex/Em range, 200-250/275-380 nm) and B (Ex/Em range, 260-320/275-360 nm), corresponding respectively to the aromatic protein region and soluble microbial by-product-like region, were identified in a three-dimensional excitation-emission matrix of EPS samples. The fluorescence peak, which corresponds to humic-like substances, was also identified though at low intensity. The ability of EPS to bind ACE was found to exceed that for ERY. The aromatic protein fraction of EPS displays a slightly higher affinity for drugs than that shown by the soluble microbial by-product-like fraction. The S-EPS and B-EPS present the same affinity for ACE and ERY. The effective quenching constants (log K) derived from the Stern-Volmer Equation equaled at peak A (with S-EPS): 3.7 ± 0.2 to 4.0 ± 0.1 for ACE and 2.1 ± 0.3 to 2.7 ± 0.1 for ERY. With B-EPS, these values were 3.9 ± 0.1 to 4.0 ± 0.1 for ACE and 2.0 ± 0.2 to 2.6 ± 0.1 for ERY. Our results suggest that the weaker EPS affinity for ERY than for ACE serves to partially explain why only about 50-80 % of ERY is removed from wastewater at the treatment plant. Moreover, this work demonstrates that EPS from natural river biofilms are able to bind drugs, which in turn may limit the mobility of drugs in natural waters.

Effects of curcumin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in rats: possible role of CYP3A4 and P-glycoprotein inhibition by curcumin.

The effects of curcumin, a natural anti-cancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, were investigated in rats. Tamoxifen and curcumin interact with cytochrom P450 (CYP) enzymes and P-glycoprotein, and the increase in the use of health supplements may result in curcumin being taken concomitantly with tamoxifen as a combination therapy to treat or prevent cancer. A single dose of tamoxifen was administered orally (9 mg x kg(-1)) with or without curcumin (0.5, 2.5 and 10 mg x kg(-1)) and intravenously (2mg x kg(-1)) with or without curcumin (2.5 and 10 mg x kg(-1)) to rats. The effects of curcumin on P-glycoprotein (P-gp) and CYP3A4 activity were also evaluated. Curcumin inhibited CYP3A4 activity with 50% inhibition concentration (IC50) values of 2.7 microM. In addition, curcumin significantly (P < 0.01 at 10 microM) enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp in a concentration-dependent manner. This result suggested that curcumin significantly inhibited P-gp activity. Compared to the oral control group (given tamoxifen alone), the area under the plasma concentration-time curve (AUC(0-infinity)) and the peak plasma concentration (C(max)) of tamoxifen were significantly (P < 0.05 for 2.5 mg x kg(-1); P < 0.01 for 10 mg x kg(-1)) increased by 33.1-64.0% and 38.9-70.6%, respectively, by curcumin. Consequently, the absolute bioavailability of tamoxifen in the presence of curcumin (2.5 and 10 mg x kg(-1)) was 27.2-33.5%, which was significantly enhanced (P < 0.05 for 2.5 mg x kg(-1); P < 0.01 for 10 mg x kg(-1)) compared to that in the oral control group (20.4%). Moreover, the relative bioavailability of tamoxifen was 1.12- to 1.64-fold greater than that in the control group. Furthermore, concurrent use of curcumin significantly decreased (P < 0.05 for 10 mg x kg(-1)) the metabolite-parent AUC ratio (MR), implying that curcumin may inhibit the CYP-mediated metabolism of tamoxifen to its active metabolite, 4-hydroxytamoxifen. The enhanced bioavailability of tamoxifen by curcumin may be mainly due to inhibition of the CYP3A4-mediated metabolism of tamoxifen in the small intestine and/or in the liver and to inhibition of the P-gp efflux transporter in the small intestine rather than to reduction of renal elimination of tamoxifen, suggesting that curcumin may reduce the first-pass metabolism of tamoxifen in the small intestine and/or in the liver by inhibition of P-gp or CYP3A4 subfamily.

Sensitive determination of tilmicosin, erythromycin ethylsuccinate and clindamycin by CE with electrochemiluminescence detection using azithromycin as internal standard and its applications.

A sensitive approach for the simultaneous determination of tilmicosin, erythromycin ethylsuccinate and clindamycin was developed by CE coupled with electrochemiluminescence detection with ionic liquid. The parameters for CE, electrochemiluminescence detection and the effect of ionic liquid were investigated systematically. The three analytes were well separated and detected within 8 min. The limits of detection (S/N=3) of tilmicosin, erythromycin ethylsuccinate and clindamycin are 3.4x10(-9), 2.3x10(-8) and 1.3x10(-8) mol/L, respectively. The precisions (RSD%) of the peak area and the migration time are from 0.8 to 1.5% and from 0.2 to 0.5% within a day and from 1.8 to 2.7% and from 0.6 to 0.8% in 3 days, respectively. The limits of quantitation (S/N=10) of tilmicosin, erythromycin ethylsuccinate and clindamycin are 3.2x10(-8), 2.9x10(-7) and 9.1x10(-8) mol/L in human urines and 5.5x10(-8), 3.2x10(-7) and 2.1x10(-7) mol/L in milk samples, respectively. The recoveries of three analytes at different concentration levels in urine, milk and drugs are between 90.0 and 104.7%. The proposed method was successfully applied to the determination of three analytes in human urine, milk and drugs.

Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis.

BACKGROUND: Current pharmacologic treatments for gastroparesis have been disappointing due to the limited options available. Erythromycin ethylsuccinate is a potent prokinetic agent that stimulates gastric emptying. Recently, erythromycin has been linked to the occurrences of sudden cardiac death due to QT prolongation. Azithromycin is similar to erythromycin in structure but does not have significant drug-drug interactions as seen with erythromycin. PURPOSE: This study aims to determine whether azithromycin stimulates antral activity in patients with chronic gastrointestinal pain and refractory gastroparesis. METHODS: Small bowel manometric data on 30 patients undergoing clinical evaluation for chronic digestive problems or documented refractory gastroparesis were reviewed. Antral activity was measured after infusion of erythromycin 250 mg intravenous and azithromycin (500 or 250 mg intravenous) given at different intervals during the small bowel manometry. The parameters measured included the total duration of effect, mean amplitude of antral contractions, duration of the highest antral contraction phase, number of cycles per minute, and the motility index. RESULTS: Comparison of erythromycin and azithromycin at similar doses showed a similar positive effect on antral activity. However, comparison of erythromycin and azithromycin at the higher dose of 500 mg showed that the mean amplitude, duration of antral activity, and motility index were significantly increased with azithromycin (P < 0.05). CONCLUSIONS: Azithromycin stimulates antral activity similar to erythromycin and moreover has a longer duration of effect. However, unlike erythromycin, azithromycin does not have significant drug-drug interactions and maybe a potential new medication for the treatment of gastroparesis and gastrointestinal dysmotility.

[Specific ototoxic effects of monomycin in immature animals].

Dynamics of the hearing function was evaluated using immature animals based on the SSCP data. Morphological characteristics of the cochlear auditory ganglion were studied after administration of therapeutic doses of the ototoxic antibiotic monomycin. Untreated animals served as controls. The results of morphofunctional investigations were evaluated in comparison with the similar data obtained in adult cats after injection of the same doses of monomycin.

Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs.

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.

Multiple aphthoid syphilitic chancres of the oral cavity.

We describe the case of a 31-year-old man who was affected by three asymptomatic, aphthoid, syphilitic chancres of the oral cavity. These lesions were accompanied by right latero-cervical and chin lymphadenopathy. The infection was previously diagnosed as aphthous stomatitis. The search for Treponema pallidum by means of darkfield microscope examination was positive. The patient was successfully treated with oral erythromycin ethylsuccinate. To our knowledge, this is the first case of multiple aphthoid syphilitic chancres of the oral cavity reported in the literature. We suggest that all patients with a recent history of painless ulcers in the oral cavity, accompanied by regional lymphadenopathy in which the clinical diagnosis has not been confirmed, should undergo a darkfield microscope examination.

[Erythromycin ethylsuccinate obtaining possibilities]. / Posibilitati de obtinere a etil-succinatului de eritromicina.

UNLABELLED: In this study we tried to improve the erythromycin ethylsuccinate obtaining, having in view to separate the erythromycin ester by crystallization in water. MATERIAL AND METHODS: The erythromycin acylation and the erythromycin ethylsuccinate crystallization were realized, following the next steps: 1. the acylation of the erythromycin with a methylene chloride solution of monoethylsuccinyl chloride, at 25-28 degrees C for 3 hours in the presence of NaHCO3; 2. the transfer of the erythromycin ethylsuccinate from methylene chloride solution in acetone solution by distillation of mixture methylene chloride: acetone 1:1 at 25-28 degrees C; 3. erythromycin ethylsuccinate separation by crystallization in water at pH = 8-8.5 and 5 degrees C for 90 minutes. The quality control for the erythromycin ester was performed according to the Xth edition of Romanian Pharmacopoeia standards using national standard for erythromycin ethylsuccinate and national standard for erythromycin with an activity of 1: 937 U and 2.02% humidity. The Micrococcus luteus ATCC 9341 was used as a test microorganism and a thin layer cromatography was performed for qualitative control. RESULTS: 13.1 g of erythromycin ethylsuccinate were obtained with an output of the process of 82.02%. Using water for the separation of erythromycin ethylsuccinate the output of the process is greater (82.02%) than in case of using petroleum ether (74.14%) or hexane (80.25%). The thin layer cromatography revealed an Rf = 0.56 and the microbiological activity of the erythromycin ethylsuccinate was 98.7% compared with the standard. CONCLUSIONS: Using water instead of hexane or petroleum ether is gainful for the separation of erythromycin ethylsuccinate from the reaction medium. The obtained erythromycin ethylsuccinate corresponds to the Xth edition of Romanian Pharmacopoeia standards. So, the raw materials consumption is decreased, the costs are cut down, the obtained product purity is high and the output of the process is greater.

Mechanism for the degradation of erythromycin A and erythromycin A 2'-ethyl succinate in acidic aqueous solution.

A major drawback of the antibiotic erythromycin A is its extreme acid sensitivity, leading to rapid inactivation in the stomach. The accepted model for degradation in aqueous acidic solution has erythromycin A in equilibrium with erythromycin A enol ether and degrading to anhydroerythromycin A. We report a detailed kinetic study of the acidic degradation of erythromycin A and of erythromycin A 2'-ethyl succinate (the market-leading pediatric prodrug), investigating the reaction rates and degradation products via NMR. This reveals that the accepted mechanism is incorrect and that both the enol ether and the anhydride are in equilibrium with the parent erythromycin. By implication, both the anhydride and enol ether are antibacterially inactive reservoirs for the parent erythromycin. The actual degradation pathway is the slow loss of cladinose from erythromycin A (or erythromycin A 2'-ethyl succinate), which is reported here for the first time in a kinetic study. The kinetic analysis is based on global, nonlinear, simultaneous least-squares fitting of time course concentrations for all species across multiple datasets to integrated rate expressions, to provide robust estimates of the rate constants.

Femtosecond IR spectroscopy of peroxycarbonate photodecomposition: S1-lifetime determines decarboxylation rate.

The ultrafast photofragmentation of arylperoxycarbonates R-O-C(O)O-O-tert-butyl (R = naphthyl, phenyl) is studied using femtosecond UV excitation at 266 nm and mid-infrared broadband probe pulses to elucidate the dissociation mechanism. Our experiments show that the rate of fragmentation is determined by the S1-lifetime of the peroxide, i.e., the time constants of S1 decay and of CO2 and R-O* formation are identical. The fragmentation times are solvent dependent and for tert-butyl-2-naphthylperoxycarbonate (TBNC) vary from 25 ps in CH2Cl2 to 52 ps in n-heptane. In the case of the tert-butylphenylperoxycarbonate (TBPC) the decomposition takes 5.5 ps in CD2Cl2 and 12 ps in n-heptane. The CO2 fragment is formed vibrationally hot with an excess energy of about 5000 cm(-1). The hot CO2 spectra at high energy can be modeled assuming Boltzmann distributions with initial vibrational temperatures of ca. 2500 K which relax to ambient temperature with time constants of 280 ps in CCl4 and 130 ps in n-heptane. In CCl4 the relaxed spectra at 1.5 ns show 3.5% residual excitation in the n = 1 level of the asymmetric stretch vibration.

Antibiotics for whooping cough (pertussis).

BACKGROUND: Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. DATA COLLECTION AND ANALYSIS: Three to four review authors independently extracted data and assessed the quality of each trial. MAIN RESULTS: Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. AUTHORS' CONCLUSIONS: Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Nondestructive quantitative analysis of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy combined with radial basis function neural networks.

A new assay method for the nondestructive determination of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy (NIR) combined with radial basis function (RBF) neural networks is investigated. The modern near-infrared spectroscopy analysis technique is efficient, simple and nondestructive, which has been used in chemical analysis in diverse fields. Short-wave NIR is a more rapid, flexible, and cost-effective method to control product concentration in pharmaceutical industry. The RBF neural networks are local approximation networks that have superiorities in function approximation and learning speed. In addition, the structure of RBF networks is simple. Estimate and calibration of the sample concentration via short-wave NIR are made with the aid of RBF models based on conventional spectra, standard normal variate (SNV), multiplicative scatter correction (MSC) and the first-derivative spectra. Various optimum models of them are established and compared. Experiment results show that the models of SNV spectra can give better performance, and the optimized RBF neural network model after SNV treatment were given, by which the root-mean-square-errors (RMSE) for calibration set and test set were 0.3266% and 0.5244%, respectively and the correlation coefficients (R) for calibration set and test set were 0.9942 and 0.9852, respectively. The proposed RBF method based on short-wave NIR is more valuable and economical for quantitative analysis than traditional methods such as partial least squares (PLS).

A validated spectrofluorometric assay for the determination of certain macrolide antibiotics in pharmaceutical formulations and spiked biological fluids.

This paper describes a simple spectrofluorometric method for the analysis of 4 macrolide antibiotics. The method is based on the condensation of 10% (w/v) malonic acid and acetic acid anhydride under the catalytic effect of tertiary amine groups of the studied macrolides. The relative fluorescence intensity of the condensation product was measured at 397/452 nm (excitation/emission) for azithromycin dihydrate and at 392/445 nm (for clarithromycin, erythromycin ethylsuccinate, and roxithromycin. All variables affecting the reaction conditions were studied. The effects of potential interference due to common excipients, such as starch, lactose, sucrose, glucose, gum acacia, and magnesium stearate, as well as trimethoprim and sulfisoxazole acetyl formulated in primomycin capsules and pediazole oral suspension, respectively, were studied. A validation study for the proposed method was carried out according to U.S. Pharmacopeia 2002. The linearity ranges were 3-80 ng/mL for all of the cited macrolides. The limit of detection range was 0.74-1.20 ng/mL, while the limit of quantitation range was 2.47-4.02 ng/mL. The method was applied for the assay of the studied macrolides in pure pharmaceutical formulations and in spiked biological fluids. Results were compared with those obtained from the reported method, where calculated t- and F-values indicated high accuracy and good precision for the proposed method.