Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

The use of cellulosic polymers as efficient reducing, coating agents, and stabilizers in the formulation of silver nanoparticles (AgNPs) with antioxidant and antibacterial activity was investigated. AgNPs were synthesized using different cellulosic polymers, polyethylene glycol, and without polymers using tri-sodium citrate, for comparison. The yield, morphology, size, charge, in vitro release of silver ion, and physical stability of the resulting AgNPs were evaluated. Their antioxidant activity was measured as a scavenging percentage compared with ascorbic acid, while their antibacterial activity was evaluated against different strains of bacteria. The amount of AgNPs inside bacterial cells was quantified using an ICP-OES spectrometer, and morphological examination of the bacteria was performed after AgNPs internalization. Cellulosic polymers generated physically stable AgNPs without any aggregation, which remained physically stable for 3 months at 25.0 ± 0.5 and 4.0 ± 0.5 °C. AgNPs formulated using ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) had significant (p ≤ 0.05; ANOVA/Tukey) antibacterial activities and lower values of MIC compared to methylcellulose (MC), PEG, and AgNPs without a polymeric stabilizer. Significantly (p ≤ 0.05; ANOVA/ Tukey) more AgNPs-EC and AgNPs-HPMC were internalized in Escherichia coli cells compared to other formulations. Thus, cellulosic polymers show promise as polymers for the formulation of AgNPs with antioxidant and antibacterial activities.

Tigecycline (TIGE) is the newest tetracycline derivative antibiotic with low toxicity, it is used for management of infectious diseases caused by Gram‐positive and Gram‐negative bacteria. Hence, an efficient, selective and sensitive method was developed for analysis of TIGE in commercial formulations, human plasma and urine. The spectrofluorimetric technique based on the reaction of secondary amine moiety in TIGE with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in slightly alkaline medium producing a highly fluorescent product measured at 540 nm (λex at 470 nm) after heating for 15 min at 75°C. The proposed strategy was upgraded and approved by ICH rules and bio‐analytical validated using US‐FDA recommendations. A linear relationship between fluorescence intensity and TIGE concentration was observed over the concentration range 40–500 ng mL−1 with limit of quantification (LOQ) 21.09 ng mL−1 and limit of detection (LOD) 6.96 ng mL−1.The ultra‐affectability and high selectivity of the proposed strategy permits analysis of TIGE in dosage form, human plasma and urine samples with good recovery ranged from 97.23% to 98.72% and from 99.36% to 99.80% respectively, without any interfering from matrix components. Also, the developed strategy was used to examine the stability of TIGE in human plasma and applied for pharmacokinetic investigation of TIGE.

Tigecycline (TIGE) is the newest tetracycline derivative antibiotic with low toxicity, it is used for management of infectious diseases caused by Gram‐positive and Gram‐negative bacteria. Hence, an efficient, selective and sensitive method was developed for analysis of TIGE in commercial formulations, human plasma and urine. The spectrofluorimetric technique based on the reaction of secondary amine moiety in TIGE with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in slightly alkaline medium producing a highly fluorescent product measured at 540 nm (λex at 470 nm) after heating for 15 min at 75°C. The proposed strategy was upgraded and approved by ICH rules and bio‐analytical validated using US‐FDA recommendations. A linear relationship between fluorescence intensity and TIGE concentration was observed over the concentration range 40–500 ng mL−1 with limit of quantification (LOQ) 21.09 ng mL−1 and limit of detection (LOD) 6.96 ng mL−1.The ultra‐affectability and high selectivity of the proposed strategy permits analysis of TIGE in dosage form, human plasma and urine samples with good recovery ranged from 97.23% to 98.72% and from 99.36% to 99.80% respectively, without any interfering from matrix components. Also, the developed strategy was used to examine the stability of TIGE in human plasma and applied for pharmacokinetic investigation of TIGE.

Abstract Ceftazidime pentahydrate (CEF) and Vancomycin hydrochloride (VAN) are antimicrobial drugs they are used worldwide especially in developing countries for management several diseases caused by bacterial infections especially against Pseudomonas species. From this point, ultrasensitive, simple, rapid, cost effective method was developed for assay of CEF and VAN in real human plasma. The proposed spectrofluorimetric method was achieved using fluorescamine reagent. This method based on reaction of fluorescamine reagent with primary amine moiety (aromatic and aliphatic) in CEF and VAN respectively, with calibration graph from 30 to 300 ng mL−1 and 0.5–30 ng mL−1 was plotted under optimum conditions. The investigated method was developed and bio-analytically validated using ICH and US-FDA recommendations. The proposed method was successfully used for determination of the cited drugs in real human plasma with high percentage of recovery ranged from 95.72 ± 0.95% to 97.72 ± 2.02 and pharmaceutical formulations with percentage 101.55 ± 0.55% and 101.99 ± 0.43% for CEF and VAN respectively. The study was also utilized to examine the stability of the CEF and VAN in real human plasma.

Abstract Ceftazidime pentahydrate (CEF) and Vancomycin hydrochloride (VAN) are antimicrobial drugs they are used worldwide especially in developing countries for management several diseases caused by bacterial infections especially against Pseudomonas species. From this point, ultrasensitive, simple, rapid, cost effective method was developed for assay of CEF and VAN in real human plasma. The proposed spectrofluorimetric method was achieved using fluorescamine reagent. This method based on reaction of fluorescamine reagent with primary amine moiety (aromatic and aliphatic) in CEF and VAN respectively, with calibration graph from 30 to 300 ng mL−1 and 0.5–30 ng mL−1 was plotted under optimum conditions. The investigated method was developed and bio-analytically validated using ICH and US-FDA recommendations. The proposed method was successfully used for determination of the cited drugs in real human plasma with high percentage of recovery ranged from 95.72 ± 0.95% to 97.72 ± 2.02 and pharmaceutical formulations with percentage 101.55 ± 0.55% and 101.99 ± 0.43% for CEF and VAN respectively. The study was also utilized to examine the stability of the CEF and VAN in real human plasma.

Abstract Doripenem monohydrate (DOR), is a recently FDA approved β- lactam antibiotic. DOR belongs to carbapenems class and it is used for the treatment of several diseases caused by different strains of bacteria. Herein, new highly sensitive, low casting, and selective spectrofluorimetric method was developed and validated for determination of DOR in real human plasma. The developed approach based on the reaction of 4-Chloro-7-nitrobenzofurazan (NBD-Cl) with secondary amine moiety in DOR using 0.1 M borate buffer at pH 8.5 producing fluorescent product measured at 535 nm (λex at 475 nm) after heating for 8 min at 70 °C. The calibration range was studied under optimum conditions and it was linear from 30 to 500 ng mL−1, with LOD 9.73 ng mL−1 and LOQ 24.05 ng mL−1. The investigated method was validated and bio-analytically validated using ICH and FDA recommendations. Moreover, the proposed method was successfully utilized to quantify DOR in a commercial formulation, human plasma and urine with high percentage of recovery in the range of 97.26% to 98.89% for plasma samples and within the range of 99.28% to 99.84% for urine samples. Further, the proposed method was successfully applied for extensive pharmacokinetic study in order to improve patient health.

Abstract Doripenem monohydrate (DOR), is a recently FDA approved β- lactam antibiotic. DOR belongs to carbapenems class and it is used for the treatment of several diseases caused by different strains of bacteria. Herein, new highly sensitive, low casting, and selective spectrofluorimetric method was developed and validated for determination of DOR in real human plasma. The developed approach based on the reaction of 4-Chloro-7-nitrobenzofurazan (NBD-Cl) with secondary amine moiety in DOR using 0.1 M borate buffer at pH 8.5 producing fluorescent product measured at 535 nm (λex at 475 nm) after heating for 8 min at 70 °C. The calibration range was studied under optimum conditions and it was linear from 30 to 500 ng mL−1, with LOD 9.73 ng mL−1 and LOQ 24.05 ng mL−1. The investigated method was validated and bio-analytically validated using ICH and FDA recommendations. Moreover, the proposed method was successfully utilized to quantify DOR in a commercial formulation, human plasma and urine with high percentage of recovery in the range of 97.26% to 98.89% for plasma samples and within the range of 99.28% to 99.84% for urine samples. Further, the proposed method was successfully applied for extensive pharmacokinetic study in order to improve patient health.

bstract Teicoplanin (TEIC) is a glycopeptide antimicrobial medication for management of several bacterial infectious diseases caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Novel, very simple, fast and cost-effective two spectrofluorimetric methods were developed for the ultra-trace determination of TEIC in pharmaceutical vials and human plasma. The investigated methods based on measuring the fluorescence of TEIC in methanol (method A) and enhancing its fluorescence by 10 folds using silver nanoparticles (AgNPs) without any solvent extraction (method B). The fluorescence of TEIC was investigated at 385nm (excitation at 335 nm) with calibration ranged from 1 to 25 ng mL−1 and from 0.6 to 30 ng mL−1 with Limit of detection (LOD) of 280 and 160 pg mL−1 for method A and B respectively. The established methods were optimized, validated and bio-analytically validated via ICH and US-FDA guidelines. The performed methods were used to determine TEIC in human plasma with high percentage recovery of 98.8 ± 1.75. Further, the proposed methods were applied to study the stability of TEIC after exposure to various degradation stress conditions and kinetic degradations.