Ciprofloxacin In Human Plasma Research Articles

Electroanalytical application of Ag@POM@rGO nanocomposite and ionic liquid modified carbon paste electrode for the quantification of ciprofloxacin antibiotic

In this work, introduction of a sensitive electrochemical nanosensor based on carbon paste electrode (CPE) modified by silver decorated in polyoxometalate (POM), reduced graphene oxide (rGO) and ionic liquid (IL) was developed for measurement of ciprofloxacin (CIP). For this purpose, Ag@POM@rGO nanocomposite was firstly prepared and identified by various methods. The peaks of C 1 s, O 1 s, P 2p, Ag 3d and W 4f in the XPS spectra confirmed formation of the Ag@POM@rGO. The effects of Ag@POM@rGO and IL amounts, pH and scan rate were examined on the response of CIP electro-oxidation by Design-Expert software. Based on the obtained results, the modified electrode with 0.01 g of IL and 0.04 g of Ag@POM@rGO in phosphate buffer solution (0.1 M, pH 7.0) with at a scan rate of 0.07 V s−1 displayed the best electrochemical response. The oxidation overvoltage of CIP was significantly reduced compared to CPE and its oxidation current was increased dramatically. In the optimum situation, the calibration curve for CIP was obtained by SWV technique and limit of detection (LOD) and linear dynamic ranges (LDR) were attained to be 0.031 µM and 0.103–122.880 µM, respectively. The electron-transfer coefficient, catalytic rate constant and diffusion coefficient were obtained to be 0.855, 3.91 × 106 cm3 mol−1 s−1 and 2.52 × 10−5 cm2 s−1, respectively. Also, the practical application of Ag@POM@rGO-IL/CPE was considered by determining the concentration of spiked CIP in human plasma with good recovery. The planned procedure is easy, fast and inexpensive and might be used as an important analytical implement in quality control of the pharmaceutical industry.

Meropenem and ciprofloxacin in complicated gastric surgery for cancer patients: A simple SPE-UHPLC-PDA method for their determination in human plasma.

A simple and rapid ultra-high-performance liquid chromatographic (UHPLC) for the simultaneous determination of meropenem and ciprofloxacin in human plasma was developed and validated. All of the analytes were separated in <5 min. A solid-phase extraction method was applied from sample preparation. Analytical separation was performed on a Poroshell SB C18 column (50 × 2.1 mm, 2.7μm particle size) with photodiode array (PDA) detection. Meropenem and ciprofloxacin were determined at wavelengths of 300 and 277 nm, respectively. The mobile phase was a mixture of acetonitrile-10 mm ammonium acetate-methanol in gradient elution. The method has been validated for both drugs in gastric surgery for cancer patients. The method showed good linearity with correlation coefficients, r2 = 0.994 for the two drugs, as well as high precision (RSD < 10.5% in each case); accuracy ranged from -5.8 to +6.0%. The limit of quantitation of the two drugs was established at 0.02 and 0.01μg/mL, respectively. Meropenem, ciprofloxacin and the internal standard were extracted from human plasma with a mean recovery ranging from 92.5 to 98.6%. The method was applied to quantify the drugs dosage in complicated gastric surgery patients.

Surfactant‐enhanced spectrofluorimetric detection after magnetic nanoparticles‐based micro‐solid‐phase extraction coupled with dispersive liquid–liquid micro‐extraction for determination of ciprofloxacin in human plasma

A sensitive and fast micro-solid-phase extraction (μ-SPE) coupled with dispersive liquid–liquid micro-extraction (DLLME) was reported before micelle enhanced spectrofluorimetric detection for determination of ciprofloxacin antibiotic in human plasma samples. The DLLME was performed using methanol as disperser and 1-octanol as extracting solvent. Oleic acid-modified Fe3O4 nanoparticles (as hydrophobic adsorbents) were applied in μ-SPE step to extract the analyte from DLLME procedure. The method uses the advantageous of high surface area and strong superparamagnetism of these nanoparticles to many avoid labourhood column/cartridge-passing processes of traditional SPE. The major parameters affecting signal enhancement and analyte recovery were evaluated and optimised. Under the optimal conditions, the calibration curve (with calibration equation of I f = 2.5826 C + 10.273) was linear in the range 0.5–600 μg L−1 (R 2 = 0.997) with low limit of detection of 0.21 µg L−1 and limit of quantification of 0.63 µg L−1. The intra-day and inter-day precisions (as relative standard deviation) were in the range of 1.01–1.67% and high recoveries in the range of 93.5–102.4% were obtained. The results demonstrated that the proposed method is easy, low cost, and accurate. In addition, it confirms that choosing extraction solvent was not restricted to the high-density solvents which can extent the versatility of DLLME.

Development and validation of a fast micro-extraction by packed sorbent UHPLC-PDA method for the simultaneous determination of linezolid and ciprofloxacin in human plasma from patients with hospital-acquired pneumonia

An ultra high-performance liquid chromatographic (UHPLC) method with PDA detection was developed and validated for the simultaneous quantification of linezolid and ciprofloxacin in human plasma and applied in hospital acquired pneumonia patients (HAP). The method uses a semi-automated microextraction by packed sorbent for sample preparation. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration - ejection cycles) and in the desorption step (percentage of acetonitrile in the solvent of elution and number of aspirations of elution solvent through the device) were statistically significant when the recovery was used as response. The method showed good linearity with correlation coefficients, r2>0.9995 for the two drugs, as well as high precision (RSD%<9.77% in each case), accuracy ranged from −6.2% to +8.2. The limit of quantification of the two drugs was established at 0.01 and 0.02μg/mL for ciprofloxacin and linezolid, respectively. Linezolid, ciprofloxacin and internal standard were extracted from human plasma with a mean recovery ranging from 92.4% to 97.4%. During validation, the concentrations of linezolid and ciprofloxacin were found to be stable after 3 freeze-thaw cycles and for at least 24h after extraction. This method will subsequently be used to quantify the drugs dosage in patients with HAP to establish if the dosage regimen given is sufficient to eradicate the infection at the target site.

A simple and sensitive high-performance liquid chromatography method for determination of ciprofloxacin in bioavailability studies of conventional and gastroretentive prolonged-release formulations.

Background:A very simple, sensitive, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet detector was developed and applied to determine ciprofloxacin in human plasma following administration of a gastroretentive formulation developed in our laboratory.Materials and Methods:HPLC analysis was performed on a C18 μ-Bondapack column (250 mm × 3.9 mm) using acetonitrile: potassium dihydrogen phosphate solution 0.1 M (20:80, v/v, pH 3) at a flow rate of 1.5 ml/min and eluate was monitored at 276 nm. After addition of phenacetin as internal standard, plasma samples were treated with 0.1 M phosphate buffer (pH: 7) and followed by extraction with dichloromethane. The method was validated for linearity, precision, accuracy, limit of quantitation (LOQ), robustness, stability, and applied in bioavailability studies of our developed gastroretentive formulation in healthy volunteers.Results:The calibration curves were linear over the concentration range 0.025–4 μg/ml with the detection limit of 15 ng/ml. Accuracy % were within 93–115 and the coefficient of variance % ranged from 0.20 to 12.8. The very low LOQ (25 ng/ml) allowed avoiding fluorometric detection which is more expensive and is not available in all laboratories. Ciprofloxacin was stable in samples with no evidence of degradation during 3 freeze-thaw cycles and 3 months storage at –70°C.Conclusion:This validated HPLC method was successfully used for the determination of ciprofloxacin in human plasma following oral administration of controlled release formulation, conventional immediate-release tablets and when administered concomitantly with divalent and trivalent cations such as aluminum-, magnesium-, or calcium-containing products under which the bioavailability of ciprofloxacin is significantly reduced.

Relative Bioavailability of Ciprofloxacin Doses (750 and 1000) mg in Healthy Male Volunteers by Using HPLC Method

A new, stable and accurate high performance liquid chromatography ultraviolet spectrophotometric method for quantitation of Ciprofloxacin in human plasma was developed and validated. The chromatographic separation was performed on a reversed phase BDS (base deactivated silica) C18 analytical column; 150 × 4.6; 5 μm particle size. The mobile phase consisted of a mixture of 1 ml triethylamine (TEA)/1L, water and acetonitrile (80:20 v/v). The pH of mobile phase was adjusted to 2.5 by using phosphoric acid and the detector was set at a wavelength of 280 nm. Accuracy, precision, linearity and stability of the analytical method were done. The regression equations are linear (R 2 was 0.999) over the calibration curve concentration range of (0.10-8.0) µg/ml. Inter and Intra precision (% CV) were less than 6.102% and 6.82% respectively.

Quantification of Ciprofloxacin in Human Plasma by Validated LC-MS/MS Using Ofloxacin as an Internal Standard and its Clinical Application

Quantification of Ciprofloxacin in Human Plasma by Validated LC-MS/MS Using Ofloxacin as an Internal Standard and its Clinical Application

A Liquid Chromatography Assay for the Simultaneous Quantification of Piperacillin and Ciprofloxacin in Human Plasma and Dialysate in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

Piperacillin/tazobactam and ciprofloxacin are often used in combination as initial empiric anti-biotic therapy in critical ill patients. Especially in patients undergoing continuous renal replacement therapy (CRRT) the pharmacokinetics of antimicrobial agents can be highly variable. In order to avoid under- or overdosage of antibiotics therapeutic drug monitoring (TDM) is highly re-commendable. Based on two known HPLC assays for piperacillin a new method in combination with solid phase extraction (SPE) for the simultaneous determination of piperacillin and ciprofloxacin was developed. Method validation was performed according to the EMA guideline on validation of bioanalytical methods. The HPLC column used was a Perfect Bond ODS-HD C18 analytical column (100 mm × 4.6 mm i.d., particle size 5 μm), equipped with a guard column (10 mm × 4.6 mm, particle size 5 μm) containing the same packing material. Detection wavelength was set at 228 nm for piperacillin and benzylpenicillin was used as internal standard (IS). Ciprofloxacin was determined at two wavelengths (280 nm, 315 nm). This newly developed HPLC method in combination with SPE-extraction allows an accurate, precise, specific and efficient determination of piperacillin and ciprofloxacin in biological matrices. Results allow the calculation of all relevant pharmacokinetic data for critically ill patients undergoing CRRT and the optimization of dosing and TDM.

Determination of Ciprofloxacin in Human Plasma and Urine by Precolumn Derivatization High Performance Liquid Chromatography with Fluorescence Detection

A sensitive, simple and selective high-performance liquid chromatographic (HPLC) method was developed for the determination of ciprofloxacin in biological fluids. The method is based on the reaction between the drug and 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a highly fluorescent derivative that is measured at 535 nm after excitation at 464 nm. The calibration curves were linear over the concentration ranges of 25–3000 and 50–3000 ng·mL−1 for plasma and urine, respectively. The mean recovery of ciprofloxacin from plasma and urine was 98.37% and 98.40%, respectively. The method was found to be sensitive, precise, accurate, and reproducible. All of the validation parameters were within the acceptance range.

Development and validation of a fast isocratic liquid chromatography method for the simultaneous determination of norfloxacin, lomefloxacin and ciprofloxacin in human plasma

A simple and fast liquid chromatographic method coupled with fluorescence detection (LC-FD) is reported, for the first time, for the simultaneous quantification of norfloxacin (NOR), ciprofloxacin (CIP) and lomefloxacin (LOM) in human plasma, using levofloxacin as internal standard (IS). Sample preparation consists of a single-step precipitation of plasma proteins followed by vortex-mixing and centrifugation. Chromatographic separation was achieved within 7 min on a reversed-phase C(18) column with a mobile phase consisting of 0.1% aqueous formic acid (pH = 3.0, triethylamine)-methanol (82:18, v/v) pumped isocratically at 1.2 mL/min. The detector was set at excitation/emission wavelengths of 278/450 nm. Calibration curves were linear (r(2) ≥ 0.994) in the range of 0.02-5.0 µg/mL, and the limit of quantification was established at 0.02 µg/mL for all analytes (NOR, CIP and LOM). The overall precision did not exceed 8.19% and accuracy was within ±10.91%. NOR, CIP and LOM were extracted from human plasma with an overall mean recovery ranged from 90.1 to 111.5%. No interferences were observed at the retention times of the analytes and IS. This novel LC-FD method enables the reliable determination of NOR, CIP and LOM in a single chromatographic run, which may be suitable to support human pharmacokinetic-based studies with those antimicrobial agents.

Determination of ciprofloxacin in human plasma using high-performance liquid chromatography coupled with fluorescence detection: Application to a population pharmacokinetics study in children with severe malnutrition

Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise measurement of plasma drug concentrations. We describe a rapid, selective and sensitive HPLC method coupled with fluorescence detection for determination of ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to plasma aliquots (200μL) prior to protein precipitation with acetonitrile. Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150mm×4.6mm i.d., 5μm particle size) maintained at 40°C. The mobile phase comprised a mixture of aqueous orthophosphoric acid (0.025M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and 7.0min, respectively. Calibration curves of ciprofloxacin were linear over the concentration range of 0.02–4μg/mL, with correlation coefficients (r2)≥0.998. Intra- and inter-assay relative standard deviations (SD) were <8.0% and accuracy values ranged from 93% to 105% for quality control samples (0.2, 1.8 and 3.6μg/mL). The mean (SD) extraction recoveries for ciprofloxacin from spiked plasma at 0.08, 1.8 and 3.6μg/mL were 72.8±12.5% (n=5), 83.5±5.2% and 77.7±2.0%, respectively (n=8 in both cases). The recovery for IS was 94.5±7.9% (n=15). The limits of detection and quantification were 10ng/mL and 20ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month when stored at −15°C to −25°C and −70°C to −90°C. This method was successfully applied to measure plasma ciprofloxacin concentrations in a population pharmacokinetics study of ciprofloxacin in malnourished children.

Methyl-β-cyclodextrin modified vascular prosthesis: Influence of the modification level on the drug delivery properties in different media

A textile polyester vascular graft was modified with methyl-β-cyclodextrin (MeβCD) to obtain a new implant capable of releasing antibiotics directly in situ at the site of operation over a prolonged period and thereby prevent post-operative infections. We investigated the influence of the curing parameters (time and temperature) that allow control of the degree of functionalization (DF) of the support by MeβCD. The inclusion of ciprofloxacin (CFX) in the MeβCD cavity was observed in solution by two-dimensional 1H NMR spectroscopy. The amount of CFX loaded on the modified graft increased with DF. Depending on the release medium (water, phosphate-buffered saline, or human plasma) and the DF of the prostheses, different kinetic profiles of release of CFX were obtained. The sustained release of CFX in human plasma was shown by microbiological assays that indicated prolonged antimicrobial activity against Staphylococcus aureus and Escherichia coli. Viability tests demonstrated the non-toxicity of MeβCD to an epithelial cell line (HPMEC), although a decrease in endothelial cell number was observed on the functionalized prosthesis, probably due to the roughness of the coating and also to the nature of the MeβCD polymer present on the surface of the fibers.

Analysis of Ciprofloxacin by a Simple High-Performance Liquid Chromatography Method

A simple and sensitive high-performance liquid chromatographic method is described for the quantitative analysis of ciprofloxacin in pharmaceuticals and human plasma. The method employs reversed-phase chromatography using an RP-C18 column with an isocratic mobile phase of acetonitrile-2% acetic acid aqueous solution (16:84, v/v), umbelliferone as an internal standard, and a flow rate of 1.0 mL/min. The UV detector is set at 280 nm. The limit of detection is 0.25 microM (S/N = 3, injection volume = 10 microL). The regression equations are linear (r > 0.9999) over a range between 0.51 approximately 130 microM for the pharmaceutical analysis of ciprofloxacin and 0.51 approximately 64.8 microM for the biological analysis of ciprofloxacin in human plasma. The intra- and inter-day relative standard deviation and relative error are less than 3.39% and 5.71%, respectively. All the recoveries are greater than 93.8%. This method is successfully applied in a pharmacokinetic study of a volunteer who receives a 500 mg ciprofloxacin tablet.

High performance liquid chromatographic determination of ciprofloxacin in human plasma and urine and its application to pharmacokinetic studies

A simple, highly sensitive and selective reversed-phase HPLC assay with UV detection for the determination of ciprofloxacin in human plasma and urine was developed and validated. The drug and internal standard, ofloxacin, were extracted from plasma or urine with isopropanol:methylene chloride (1:9, v/v) and back extracted with orthophosphoric acid. Separation was achieved on a C18 reversed-phase column with a mobile phase of acetonitrile:methanol:0.1M sodium dihydrogen orthophosphate:triethylamine:glacial acetic acid (8:10:83:1:2, v/v) and UV detection at 278 nm. The chromatograms were free from interference at the retention times of ciprofloxacin and the internal standard while both compounds eluted as completely resolved peaks. The calibration curves were linear (r2 %ge; 0.996) over concentration ranges of 0.01 to 3.0 µg/ml in plasma and 0.05 to 5.0 µg/ml in urine. The method was reproducible with coefficients of variation 98% in both plasma and urine. The method was successfully applied to estimate the pharmacokinetics of ciprofloxacin after oral administration of a 500 mg dose of ciprofloxacin tablets to 12 healthy volunteers. Key words: Ciprofloxacin; Reversed-phase HPLC; Pharmacokinetics; Ofloxacin Journal of Pharmacy and Bioresources Vol. 2 (1) 2005: 55-64

인체 혈장에서 염산시프로플록사신(시프로플록사신으로서 250 mg) 정량을 위한 HPLC 분석법의 유효성검토

A simple HPLC method with ultraviolet detection of ciprofloxacin in human plasma was developed and validated. After protein precipitation with trichloroacetic acid, chromatographic separation of ciprofloxacin in plasma was achieved at with a column and methanol-phosphate mixture (pH 2.5), as mobile phase. Quantitative determination was performed by ultraviolet detection at 278 nm. The method was specific and validated with a limit of quantification of 100 ng/ml. The intra- and inter-day coefficients of variation were between 1.67% and 10.55% and accuracy between 92.01 % and 106.09%. The method has been successfully applied in a bioavailability study of 250 mg ciprofloxacin hydrochloride tablet.

Simple High-Performance Liquid Chromatographic Method for Determination of Ciprofloxacin in Human Plasma

Arapid, simple and sensitive high-performance liquid chromatography method was developed for determination of ciprofloxacin in plasma by means of ultraviolet detection. Ofloxacin was used as an internal standard and separation carried on a Novapak C18 column using a mobile phase of 0.01 M phosphate buffer (pH =2.6): methanol (82:18 v/v). Extraction of drug was performed from plasma by liquid-liquid extraction and the average recovery was 78.2% The assay is precise, with inter-assay coefficient of variation of 6.70 % at 0.25-8 kg/ml (n=3). Using UVdetection at 277 nm the detection limit for ciprofloxacin was 20 ng/ml of plasma and the mean extraction recovery was 78.2 %. Short elution time, using UVdetector and usage of ofloxacin as internal standard are advantages of this method

Validation of an HPLC method for the determination of ciprofloxacin in human plasma

A simple HPLC method with fluorescence detection of ciprofloxacin in human plasma was developed and validated. After protein precipitation, chromatographic separation of ciprofloxacin in plasma was achieved at 35 °C with a C18 column and acetonitrile–phosphate mixture, pH 3, as mobile phase. Quantitative determination was performed by fluorimetry after excitation at 278 nm. The method was specific and validated with a limit of quantification of 41 ng/ml. The intra- and inter-day coefficients of variation were between 0.5 and 6.6% and accuracy between −2.02 and 7.04%. Ciprofloxacin was stable in plasma for 40 days at −20 °C and after three freezing-thawing cycles. The method has been applied in a bioequivalence study of two formulation of 500 mg ciprofloxacin.

Simple high-performance liquid chromatographic assay for the determination of ciprofloxacin in human plasma with ultraviolet detection

A simple high-performance liquid chromatographic method is described for the quantitative analysis of ciprofloxacin in human plasma. Following protein precipitation from plasma by means of 6% perchloric acid, the upper layer which contains the analyte and the internal standard lomefloxacin, was analysed on a reverse phase column LiChrospher ® 60 RP-select B (5 μm) (EcoCART ® 125-3) with ultraviolet detection at 280 nm. The mobile phase was acetic acid 5%-methanol–acetonitrile (90:5:5, v/v/v). The assay was linear for ciprofloxacin over the concentration range of 0.050 to 6.00 μg ml −1. The limit of quantification (LOQ) was 0.050 μg ml −1. The method was successfully applied to a bioavailability study with five different ciprofloxacin formulations.

Simultaneous determination of theophylline, enoxacin and ciprofloxacin in human plasma and saliva by high-performance liquid chromatography.

A simple reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous determination of theophylline, ciprofloxacin and enoxacin in plasma and saliva. The biological fluid samples were extracted with methylene chloride-isopropyl alcohol prior to isocratic chromatography on a Waters C18 mu Bondapak column. Ultraviolet detection was carried out at 268 nm. The assay is linear for ciprofloxacin and enoxacin (0.05-10 micrograms/ml), and theophylline (0.1-20 micrograms/ml). The assay can be used to investigate the interaction of these two fluoroquinolones with theophylline.

Measurement of Ciprofloxacin in Human Plasma, Whole Blood, and Erythrocytes by High-Performance Liquid Chromatography

A simple, rapid, and accurate high-performance liquid chromatographic method using fluorescence detection is described for the measurement of ciprofloxacin in plasma, whole blood, and erythrocytes. Ciprofloxacin and the internal standard difloxacin were separated on a mu-Bondapak C18 column (30 cm x 3.9 mm inside diameter, 10 microns particle size), using a mobile phase of 0.1 M phosphate buffer (pH 2.5):acetonitrile (75:25, vol/vol). The retention times were 5.1 min for ciprofloxacin and 7.9 min for difloxacin. The compounds were extracted from the three biological fluids using protein precipitation followed by a single-step liquid-liquid extraction. The assay is precise, with interassay coefficients of variation of less than or equal to 9.1% and an accuracy of less than or equal to 7.4% at 0.5 and 5.0 micrograms/ml (n = 5). The mean extraction recoveries of ciprofloxacin in plasma, whole blood, and erythrocytes were 84.4, 63.9, and 48.0%. The limit of detection for ciprofloxacin is 25 ng/ml. Ciprofloxacin concentrations in the three biological fluids were measured in patients with uncomplicated falciparum malaria to demonstrate the application of the method.