scholarly journals Quantification of Fosfomycin in Combination with Nine Antibiotics in Human Plasma and Cation-Adjusted Mueller-Hinton II Broth via LCMS

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Kelvin Kau-Kiat Goh ◽  
Wilson Ghim-Hon Toh ◽  
Daryl Kim-Hor Hee ◽  
Edwin Zhi-Wei Ting ◽  
Nathalie Grace Sy Chua ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Human Plasma ◽  
Limit Of Detection ◽  
Synergistic Activity ◽  
Limit Of Quantification ◽  
Mueller Hinton ◽  
Antibiotic Drug ◽  
Dosing Regimens ◽  
Antibiotic Combination

Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative bacteria (CRGNB). The ability to simultaneously measure fosfomycin and other antibiotic drug levels will support in vitro and clinical investigations to develop rational antibiotic combination dosing regimens against CRGNB infections. We developed an analytical assay to measure fosfomycin with nine important antibiotics in human plasma and cation-adjusted Mueller–Hinton II broth (CAMHB). We employed a liquid-chromatography tandem mass spectrometry method and validated the method based on accuracy, precision, matrix effect, limit-of-detection, limit-of-quantification, specificity, carryover, and short-term and long-term stability on U.S. Food & Drug Administration (FDA) guidelines. Assay feasibility was assessed in a pilot clinical study in four patients on antibiotic combination therapy. Simultaneous quantification of fosfomycin, levofloxacin, meropenem, doripenem, aztreonam, piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam, cefepime, and tigecycline in plasma and CAMHB were achieved within 4.5 min. Precision, accuracy, specificity, and carryover were within FDA guidelines. Fosfomycin combined with any of the nine antibiotics were stable in plasma and CAMHB up to 4 weeks at −80 °C. The assay identified and quantified the respective antibiotics administered in the four subjects. Our assay can be a valuable tool for in vitro and clinical applications.

ESTIMATION OF TADALAFIL IN HUMAN PLASMA BY SPECTROFLUOROPHOTOMETRY

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (06) ◽  
pp. 60-63
Author(s):  
Sadhana Rajput ◽  
◽  
Samir Patel ◽  
Keyword(s):  
Human Plasma ◽  
Fluorescence Spectrum ◽  
Drug Monitoring ◽  
Limit Of Detection ◽  
Wave Length ◽  
Excitation Wavelength ◽  
Limit Of Quantification ◽  
Pharmacokinetic Investigation ◽  
Satisfactory Recovery

A new, specific, selective, simple, rapid and inexpensive spectrofluorophotometric method has been developed for the determination of tadalafil in spiked human plasma. The fluorescence spectrum of tadalafil in 0.1M methanolic sulphuric acid showed excitation wavelength at 315 nm and emission wave-length at 332 nm. The method for tadalafil was found to be linear over the concentration range of 10-50 ng/mL with a correlation coefficient of 0.9991. Limit of detection and limit of quantification were found to be 0.235 ng/mL and 0.701 ng/mL, respectively. The method was validated and found to be suitable for the estimation of tadalafil from human plasma. Satisfactory recovery of tadalafil from the human plasma suggests no interference of any debris present into human plasma. This method can be used to deter-mine plasma tadalafil concentration in drug monitoring or pharmacokinetic investigation.

scholarly journals Development of the UV Spectrophotometric Method of Azithromycin in API and Stress Degradation Studies

2016 ◽  
Vol 68 ◽  
pp. 48-53 ◽  
Author(s):  
Sandip Bhimani ◽  
Gaurav Sanghvi ◽  
Trupesh Pethani ◽  
Gaurav Dave ◽  
Vishal Airao ◽  
...  
Keyword(s):  
Linear Relationship ◽  
Spectrophotometric Method ◽  
Phosphate Buffer ◽  
Macrolide Antibiotic ◽  
Limit Of Detection ◽  
High Sensitivity ◽  
Limit Of Quantification ◽  
Absorbance Maximum ◽  
Antibiotic Drug ◽  
Stress Degradation

Azithromycin (AZI) is a semi-synthetic macrolide antibiotic drug, effective against a wide variety of bacteria. The present study describes a simple, accurate, reproducible and precise UV Spectrophotometric method for the estimation of AZI (pH 6.8 Phosphate buffer). The absorbance maximum (λmax) for AZI was found to be 208nm. The method reveals high sensitivity, with linearity in the 10 µg/ml to 50 µg/ml range. The lower limit of detection was found to be 1.6µg/ml and the limit of quantification was found to be 5µg/ml. All the calibration curves demonstrated a linear relationship between the absorbance and concentration, with the correlation coefficient higher than 0.99. The % recovery was found to be 99.72%. AZI was also subjected to stress degradation under different conditions recommended by the International Conference on Harmonization (ICH).

HPTLC Separation of a Hepatoprotective Combination in Pharmaceutical Formulation and Human Plasma

2020 ◽  
Vol 58 (5) ◽  
pp. 411-417
Author(s):  
Maimana A Magdy ◽  
Rehab M Abdelfatah
Keyword(s):  
Human Plasma ◽  
High Performance ◽  
Limit Of Detection ◽  
Pharmaceutical Formulation ◽  
Limit Of Quantification ◽  
Ich Guidelines ◽  
Spiked Plasma ◽  
Significant Difference ◽  
Developing System

Abstract A binary mixture of Silymarin (SR) and Vitamin E (VE) acetate, of an antioxidant and a hepatoprotective effect, has been analyzed using a sensitive, selective and economic high performance thin layer chromatographic (HPTLC) method in their pure forms, pharmaceutical formulation and spiked human plasma. SR and VE were separated on 60F254 silica gel plates using hexane:acetone:formic acid (7:3:0.15, v/v/v) as a developing system with UV detection at 215 nm. The method was evaluated for linearity, accuracy, precision, selectivity, limit of detection (LOD) and limit of quantification (LOQ). SR and VE were detected in the linear range of 0.2–2.5 and 0.2–4.5 μg/band, respectively. Method validation was done as per ICH guidelines and acceptable results of accuracy of 99.86 ± 1.190 and 100.22 ± 1.609 for SR and VE, respectively were obtained. The method has been successfully applied for determination of the studied drugs in their pharmaceutical formulation without any interference from excipients, and in spiked plasma samples. Results obtained by the developed HPTLC-densitometric method were statistically compared to those obtained by the reported HPLC methods and no significant difference was found between them.

scholarly journals DEVELOPMENT AND EVALUATION OF NOVEL ESTIMATION TECHNIQUES FOR IN VITRO DISSOLUTION STUDY AND VALIDATION PROTOCOL FOR ESCITALOPRAM AS ANTIDEPRESSANT DRUG AND THEIR FORMULATION

2020 ◽  
pp. 55-61
Author(s):  
SHRIRAM H. BAIRAGI ◽  
R. S. GHOSH
Keyword(s):  
Limit Of Detection ◽  
Antidepressant Drug ◽  
Correlation Factor ◽  
In Vitro Dissolution ◽  
Linear Calibration ◽  
Limit Of Quantification ◽  
Minimum Concentration ◽  
Dissolution Study ◽  
Relative Standard

Objective: To develop and validate the RP-HPLC method and in vitro dissolution study for escitalopram as antidepressant drug and their formulation. Methods: The chromatographic separation was done by using a C-18, 150 mm column and a mobile phase consisting of phosphate buffer (40%) and acetonitrile HPLC grade (60%). Detection was carried out at 211 nm with a flow rate of 1 ml/min with an injection of 20 μl. The method was validated with different parameters such as linearity, precision, accuracy, robustness, and limit of detection (LOD), the limit of quantification (LOQ) according to ICH guidelines. Results: The linear calibration curve was obtained in the concentration range of 0-50 μg/ml and gave an average correlation factor 0.992. The retention time was observed at 2.96 min. The Minimum concentration level at which the analyte can be reliably detected (LOD) and quantified (LOQ) were found to be 0.03 and 0.09 µg/ml, respectively. The relative standard deviation of intra and the inter-day assay was found to be less than 2. The dissolution studies show moderate dissolution (23.4%) after 45 min, but it reaches a plateau after approximately 25 min. Conclusion: This method was found to be simple, rapid and economic with less run time. The validated parameters manifest the method is reliable, linear, accurate and precise as well as robust with minor variations in chromatographic parameters. Therefore, the developed method can be applied for both routine analysis and quality control assay and it could be a very powerful tool to investigate the stability of escitalopram.

scholarly journals In VitroCombination of Isavuconazole with Micafungin or Amphotericin B Deoxycholate against Medically Important Molds

2014 ◽  
Vol 58 (11) ◽  
pp. 6934-6937 ◽  
Author(s):  
Aspasia Katragkou ◽  
Matthew McCarthy ◽  
Joseph Meletiadis ◽  
Vidmantas Petraitis ◽  
Patriss W. Moradi ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Aspergillus Terreus ◽  
Synergistic Activity ◽  
Content Type ◽  
Amphotericin B Deoxycholate ◽  
Combination Studies

ABSTRACTWhether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Ourin vitrocombination studies showed that isavuconazole and micafungin are synergistically active againstAspergillus fumigatus,Aspergillus flavus,Aspergillus terreus, andCunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation.

scholarly journals Anti-Leukemic Effect of Retinoic Acid in Non-APL AML Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2805-2805
Author(s):  
Yasuhiko Harada ◽  
Yuichi Ishikawa ◽  
Naomi Kawashima ◽  
Hikaru Hattori ◽  
Yohei Yamaguchi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Combination Therapy ◽  
Research Funding ◽  
Gene Mutations ◽  
Synergistic Activity ◽  
Npm1 Mutation ◽  
Ic50 Value ◽  
Ic50 Values

Abstract [Background] Differentiation therapy with retinoic acid (RA) has remarkably improved the cure rate for acute promyelocytic leukemia (APL). RAs are known to have anti-leukemic effect in parts of non-APL acute myelocytic leukemia (AML) cells. It has been reported that AML patient with NPM1 or IDH1/2 mutation may have sensitivity to all-trans retinoic acid (ATRA) and the clinical study with combination of chemotherapy and ATRA is conducted in NPM1 mutated AML. In addition, ATRA and a FLT3 inhibitor, quizartinib, showed synergistic activity against FLT3-ITD positive AML patients' samples and their combination therapy improved the survival of AML xenograft mouse model. Moreover, it is also reported that the presence of super-enhancer at RARA gene locus is related to high RARA mRNA expression and sensitivity to tamibarotene. Another study showed that ATRA promote cancer apoptosis in the presence of Cellular Retinoic Acid-Binding Protein 1 (CRABP1) through G1 expansion. However, the efficacy of RAs and its mechanism in non-APL AML are still largely unknown. In this study, we evaluated anti-leukemic effect of RAs on primary AML cells and explored its predictive biomarkers for the purpose of optimization of therapy for non-APL AML. [Method] We examined growth inhibitory and differentiation effects of ATRA and tamibarotene on primary AML cells in vitro. Primary AML cells were purified by density-based centrifugation and cultured with various concentrations of RAs in methylcellulose-based media including cytokines. IC50 values of RAs were calculated by luminescent cell viable assay on day7 and 14. Cell differentiation upon RAs treatment was also examined in these cells by morphology and expression of CD11b using flow cytometry analysis. We also evaluated the efficacy of combination therapy of RAs and several tyrosine kinase inhibitors, quizartinib, midstaurin and dasatinib, and assessed their synergistic effect by calculating combination index. The association of IC50 values of RAs with clinical characteristics, mRNA expressions of RARA and CRABP1, and genetic mutations were investigated. [Result] We analyzed total of 30 primary non-APL AML samples and IC50 values of ATRA and tamibarotene were lower than 5 µM in 14 of 30 (46.7 %) and 4 of 14 (28.6 %) AML cells, respectively. There were no significant difference in IC50 value of ATRA and tamibarotene by FAB subtype and chromosomal abnormalities. ATRA and tamibarotene induced differentiation in 10 of the 22 and 2 of the 9, respectively, and anti-leukemic effect of ATRA and tamibarotene were not associated with these differentiation statuses. IC50 value of ATRA and tamibarotene were significantly lower in ASXL1 (p=0.0071 and p=0.0012, respectively), SRSF2 (p=0.0101 and p=0.0113, respectively), and IDH2 (p=0.0295 and p=0.0044, respectively) mutated AML cells. FLT3-ITD mutation with high allelic ratio (>0.5) was associated with high IC50 value of ATRA (p=0.0116). Although NPM1 mutation was associated with higher IC50 value of ATRA, all of 4 patients with NPM1 mutation concurrently have FLT3-ITD mutations in this study. Other gene mutations were not correlated with RAs sensitivity. The expression of RARA mRNA weakly correlated with sensitivity of ATRA and tamibarotene (P=0.1126 and P=0.0711 respectively), but it was not significant. [Conclusion] RAs were effective in almost half of non-APL AML cells in vitro and some AML cells were sensitive to ATRA without cell differentiation. Mutation in ASXL1, SRSF2, and IDH2 were identified as predictive factors for the RAs sensitivity, whereas the expression of RARA mRNA and other gene mutations were not correlated with RAs sensitivity. Disclosures Kiyoi: Takeda Pharmaceutical Co., Ltd.: Research Funding; Phizer Japan Inc.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Novartis Pharma K.K.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene Corporation: Research Funding; Astellas Pharma Inc.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding.

scholarly journals Micellar Enhanced Spectrofluorimetric Method for the Determination of Ponatinib in Human Plasma and Urine via Cremophor RH 40 as Sensing Agent

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Hany W. Darwish ◽  
Ahmed H. Bakheit ◽  
Ali Saber Abdelhameed ◽  
Amer S. AlKhairallah
Keyword(s):  
Human Plasma ◽  
Fluorescence Intensity ◽  
Limit Of Detection ◽  
Biological Fluids ◽  
Great Success ◽  
Limit Of Quantification ◽  
Human Plasma And Urine ◽  
Spectrofluorimetric Method ◽  
Fluorescence Characteristics

An impressively simple and precise spectrofluorimetric procedure was established and validated for ponatinib (PTB) quantitation in biological fluids such as human plasma and human urine. This method depends on examining the fluorescence characteristics of PTB in a micellar system of Cremophor RH 40 (Cr RH 40). Cr RH 40 enhanced the intrinsic fluorescence of PTB distinctly in aqueous water. The fluorescence spectra of PTB was recorded at 457 nm following its excitation at 305 nm. Maximum fluorescence intensity was attained by addition of 0.7 mL of Cr RH 40 and one mL of phosphate buffer to PTB aliquots and then dilution with distilled water. There is a linear relationship between the fluorescence intensity of PTB and its concentration over the range 5–120 ngmL−1, with limit of detection and limit of quantification equal to 0.905 ngmL−1and 2.742 ngmL−1, respectively. The accuracy and the precisions of the proposed method were checked and gave adequate results. The adopted method was applied with a great success for PTB quantitation in different biological matrices (spiked human plasma and urine) giving high recovery values.

scholarly journals A new liquid phase microextraction method-based reverse micelle for analysis of dexketoprofen in human plasma by HPLC-DAD

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dönay Yuvali ◽  
Erkan Yilmaz ◽  
İbrahim Narin
Keyword(s):  
Liquid Phase ◽  
Human Plasma ◽  
Reverse Micelle ◽  
Limit Of Detection ◽  
Aqueous System ◽  
Aqueous Sample ◽  
Photodiode Array Detection ◽  
Limit Of Quantification ◽  
Liquid Phase Microextraction ◽  
Relative Standard

AbstractA new liquid phase microextraction method was developed by used reverse micelle-based coacervates as microextraction agents for the separation of dexketoprofen (DKT) from human plasma before its determination by high-performance liquid chromatography with photodiode-array detection (HPLC-DAD). The change in the concentration of dexketoprofen in the plasma of the male and female patients was successfully monitored by using this method. The proposed method involves the use of reverse micelles of decanoic acid (DA) are dispersed in tetrahydrofuran (THF) and aqueous system. After addition of the DA and THF to the aqueous sample phase, the formation of micelles of nano and molecular size was observed in an ultrasonic bath. The solution was centrifuged, and the DKT extracted into the DA phase was analyzed by HPLC-DAD. Some analytical parameters that important in the developed procedure were examined in detail. The limit of detection (LOD), the limit of quantification (LOQ), the intraday, and inter day relative standard deviation (RSD, %) of the developed method in the plasma sample were found to be 12.8 ng mL−1, 38.8 ng mL−1, 1.7 and 3.9%, respectively. Additional/recovery studies were performed in plasma samples with proposed method, and quantitative recoveries were obtained in the range of 97–100%. The developed microextraction method was applied to human plasma that taken from volunteer patients for the determination of DKT. Graphical abstract

scholarly journals Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 8 (12) ◽  
pp. 1964
Author(s):  
Ya-Ting Chang ◽  
Tsung-Ying Yang ◽  
Po-Liang Lu ◽  
Shang-Yi Lin ◽  
Liang-Chun Wang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Therapeutic Option ◽  
Rapid Evolution ◽  
Toxicity Testing ◽  
World Health ◽  
Synergistic Activity ◽  
Carbapenem Resistant

Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP.

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