Simple and rapid high-performance liquid chromatography method for the determination of ofloxacin concentrations in plasma and urine

A high-performance liquid chromatographic method for the determination of ofloxacin in human plasma and urine was developed. The method involved deproteinisation of the sample with perchloric acid and analysis of the supernatant using a reversed-phase C column and fluorescence detection at an excitation wavelength of 290 nm and an emission wavelength of 18 460 nm. The assay was linear from 0.5 to 10.0 mg/ ml. The relative standard deviation of intra- and inter-day assays was lower than 5%. The average recovery of ofloxacin from plasma was 93%. The method was evaluated in samples from healthy subjects whose drug levels were already measured by microbiological assay. Ó 2001 Elsevier Science B.V. All rights reserved

Disposition of uric acid upon administration of ofloxacin alone and in combination with other anti-tuberculosis drugs

Disposition of uric acid upon administration of ofloxacin (O) alone and in combination with other anti-tuberculosis drugs, rifampicin (R), isoniazid (H) and pyrazinamide (Z) was studied. Twelve male healthy volunteers were investigated on four different occasions with the four drugs alone or in combinations. A partially balanced incomplete block design was adopted and the subjects were randomly allocated to each group. Uric acid concentration in urine samples excreted over 0-8 hr, were determined after coding the samples. There was significant decrease in the group receiving Z when compared to other groups. Though there was a decrease in uric acid excretion in the group receiving O, it was not statistically significant. Rifampicin and H seem to increase the uric acid excretion. The incidence of arthralgia was mainly due to Z and not due to either O or other drugs in the treatment of pulmonary tuberculosis

Ofloxacin pharmacokinetics in saliva

Objective: To study the pharmacokinetics of ofloxacin using salivary drug concentration when administered alone or in combination with rifampicin (R), isoniazid (H) and pyrazinamide (Z) and also to assess the saliva to plasma concentration ratio. Material and Methods: Twelve healthy male volunteers were investigated on four different occasions with an interval of at least one week between occasions. They were administered ofloxacin, either alone or in combination with R, H and Z. A partially balanced incomplete block design was adopted and the subjects were randomly allocated to each group. Salivary and plasma concentrations of ofloxacin were measured at 1, 2, 3, 6 and 8 h after drug(s) administration using validated methods. Results: There were no significant differences between various pharmacokinetic parameters when ofloxacin was administered alone or in combination with R, H and Z. The mean saliva to plasma ratio of ofloxacin concentration was around 0.6. The bioavailability indices of ofloxacin in the saliva and plasma were similar in all the groups. Conclusion: Several pharmacokinetic parameters could be calculated using salivary concentrations of ofloxacin. The determination of ofloxacin levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies

Survey on Network Coding for Multiple Cloud Storage

Reliability of data can be provided by maintaining redundancy in multiple cloud storage nodes. The simplest form of providing redundancy is replication, where it involves directly replicating data to multiple clouds. However, replication technique involves high computational cost and monetary cost is high when retrieving data in the multiple cloud environments. Therefore, striping data across multiple cloud storage is one of the best solution for providing redundancy and repair cost is very less when compared to replication. There exists many codes, which performs striping of data, erasure coding is an example where provides good redundancy. However, the erasure codes perform recovery of whole file rather a single block. Therefore new design problem arises when erasure codes are used. However, regenerating codes shows better solution for this problem. DOI: 10.17762/ijritcc2321-8169.15031

A RAPID ISOCRATIC HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC-UV) METHOD FOR THE QUANTIFICATION OF RITONAVIR IN HUMAN PLASMA

Objective: An accurate, simple, and rapid HPLC-UV based method for the quantitative determination of ritonavir (RTV) in human plasma is developed.Methods: The method involved deproteinization of the sample with 0.125N NaOH and methyl tertiary butyl ether and evaporated to dryness. The residue was reconstituted with mobile phase (20 mM Sodium Acetate and Acetonitrile–55:45 v/v). The analysis was done using C8 column (250 x 4.6 mm ID) and detection at a wavelength of 212 nmResults: The method range was linear over the range 0.5–10.0 µg/ml as derived using calibration curve method. Mean intra-and inter-day variations over the ranges of the standard curves were less than 10 % and mean extraction recoveries from human plasma ranged from 96 to 110 %.Conclusion: A rapid and accurate method for quantitation of RTV in plasma was validated. The assay spans the concentration range of clinical interest. The easy sample preparation and small sample size makes this assay highly suitable for pharmacokinetic studies of RTV in HIV-infected patients with TB.Keywords: Ritonavir, Pharmacokinetics, HPLC, Plasma extraction, HI

SIMULTANEOUS METHOD FOR THE ESTIMATION OF BEDAQUILINE AND DELAMANID IN HUMAN PLASMA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: A specific, simple and sensitive high-performance liquid chromatographic method for the estimation of Bedaquiline (BDQ) and Delamanid (DLM) in human plasma was developed. Methods: The method involved deproteinization and further extracted the analyte using Solid Phase Extraction (SPE) cartridge and analysed using C18 column with the wavelength set at 231 nm. The isocratic mobile phase consisted of 10 mmol ammonium acetate buffer containing 0.25% acetic acid and 0.02% trifluoroacetic acid and acetonitrile in the ratio of 20:80(v/v). The validation parameters were evaluated. The method was applied to estimate plasma BDQ and DLM collected from five MDR-TB patients. Results: Well resolved peaks of BDQ and DLM at retention times of 5.4 and 2.6 min were obtained respectively. The calibration curve was linear over a range of 0.01–10.0 µg/ml for both BDQ and DLM. The intra-and inter-day relative standard deviations for standards were below 10%. The recoveries for BDQ ranged from 101% to 107% and 98% to 107 % for DLM respectively. Conclusion: A specific and sensitive method for simultaneous determination of BDQ and DLM in plasma using high-performance liquid chromatography was developed. This method can be used in clinical studies to evaluate drug exposure

Dose related pharmacokinetics of ofloxacin in healthy volunteers

OBJECTIVE: To evaluate the pharmacokinetic profile of ofloxacin in healthy volunteers after single oral doses of 600 and 800 mg. DESIGN: Seven healthy volunteers were administered 600 and 800 mg of ofloxacin on two occasions with an interval of one week. Paired samples of blood and saliva were collected after 1, 2, 3, 6, 9, 12, 24, 32 and 48 hours post-dose. Urine samples were collected over a period of 0–6, 6–12 and 12–24 hours. Concentrations of ofloxacin in plasma, saliva and urine were assayed by high performance liquid chromatography. RESULTS: Increases of 22% in peak plasma concentration (Cmax) and 40% in area under the concentrationtime curve (AUC0–24) were observed with the 800 mg dose. The other parameters, namely time to attain Cmax, half-life, the apparent volume of distribution, plasma and renal clearance and percentage of dose excreted in urine over 24 hours were independent of doses. The mean ratios of the concentration in saliva to the concentration in plasma ranged from 0.4–0.6, and the correlation coefficient was 0.94. CONCLUSIONS: Dose proportionality was observed in Cmax and AUC0–24 when 600 and 800 mg doses of ofloxacin were given. Ofloxacin determined in saliva seems to be suitable for therapeutic drug monitoring

QUANTITATION OF METFORMIN IN URINE BY RP-HPLC METHOD AND ITS APPLICATION IN PHARMACOKINETICS

Objective: To develop and validate an easy and sensitive HPLC method for quantitation of metformin in urine. Methods: The technique involved deproteinisation of urine sample with methanol and analysis of the supernatant the usage of Zorbax 300–SCX, 4.6 X 150 mm ID, 5 µm particle size and UV detection at a wavelength of 233 nm. Results: The assay was specific for metformin and linear from 1.25 to 50.0μg/ml. The relative standard deviation of intra-and inter-day assays was lesser than 7%. The recovery of metformin from urine ranged from 97-103%. Conclusion: An easy and sensitive HPLC approach for quantitation of metformin in urine had been developed. Due to its simplicity in sample preparation and instrumentation, this technique can be used for pharmacokinetic studies of metformin in urine samples

Single Dose Pharmacokinetics of Efavirenzin Healthy Indian Subjects

Background & Objective: Access to antiretroviral therapy in India is improving. Efavirenz (EFV) is a commonly used non-nucleoside reverse transcriptase inhibitor used to treat HIV infection. No information is available on the pharmacokinetics of EFV in Indian subjects. The aim of this study was to obtain information on single dose pharmacokinetics of efavirenz (EFV) in healthy Indian subjects. Methods: Sixteen adult healthy volunteers (8 males and 8 females) were administered a single oral tablet of 600 mg EFV after an overnight fast. Blood samples were collected at 1, 2, 3, 4, 5, 6, 10, 24 and 48 hours post dosing. Plasma EFV concentrations were estimated by HPLC, and certain pharmacokinetic variables were calculated. Results: Plasma EFV concentrations were higher in females than males at all the time points, the differences being significant at 1 (p<0.001) and 2 (p=0.05) hours. Females had significantly higher peak concentration (Cmax) of EFV than males (p=0.05) (3.11 & 1.90 μg/ml). The inter-individual variability in Cmax and AUC0-48 were 42 and 45% respectively. Conclusions: This study provides basic information on the pharmacokinetics of EFV in Indian subjects. Females had higher peak levels of EFV than males. Inter-subject variability was high. Further studies are necessary to describe the pharmacokinetic profile of EFV under steady state conditions in Indian patients on antiretroviral treatment

Urine nevirapine as a predictor of antiretroviral adherence

Background & objectives: Incomplete adherence is a major contributor to failure of antiretroviral therapy. Although the available methods to monitor adherence to therapy have proved to be predictive of outcomes, the results are variable. We assessed the feasibility of detecting nevirapine (NVP) in spot urine samples to monitor patient adherence to antiretroviral treatment and to study the urinary excretion of NVP in healthy volunteers after oral administration of a single dose of NVP (200 mg). Methods: Spot urine samples were collected from 50 HIV-infected patients (36 on treatment regimen containing NVP and 14 on drugs other than NVP) and tested for NVP by HPLC in a blinded manner. Sixteen healthy volunteers (9 males and 7 females) were administered a single oral dose of 200 mg NVP and spot urine samples were collected on day ‘0’ before drug administration, and thereafter every 24 h up to 9 days and tested for NVP. Results: All the urine samples collected from patients undergoing treatment with NVP-containing regimens at different time points after drug administration tested positive for NVP. Thirteen out of 14 samples from patients not on NVP yielded a negative result. The drug was detected in the urine of healthy volunteers up to 9 days. The urinary excretion of NVP was prolonged in females than in males. Interpretation & conclusion: In view of its long half-life, NVP gets excreted in urine for a long period of time. Hence, testing spot urine samples for NVP may not be a useful measure to monitor patient adherence to treatment