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1.
An ultrafast liquid chromatographic bioanalytical method was developed and validated for the determination of telaprevir in Wistar albino rat serum. Principles of quality by design (QbD) were implemented for enhancing the bioanalytical liquid–liquid extraction of telaprevir from rat serum. A Box–Behnken design was utilized in the studies by selecting extraction time, centrifugation speed, and vortex time as the critical method variables for evaluating their effect on the critical analytical attribute, i.e., %recovery of telaprevir. Chromatographic separation was achieved within a run time of 10?min using a C-18 column and mobile phase comprising of methanol:borate buffer of pH 9 (90:10 v/v) flowing at 1.2?mL/min. Photodiode array detection was performed at 270?nm. Results of validation studies were satisfactory. The method was linear over a concentration of 25–10,000?ng/mL. Limit of detection for the developed method was 10?ng/mL. Further, design of experiments (DoE) used for inter-day accuracy and precision study suggested superior method reliability. This integrated QbD- and DoE-based approach ensured the development of a validated and reliable analytical method for optimum bioanalysis of telaprevir in biological matrix.  相似文献   

2.
A sensitive and rapid method based on alcohol‐assisted dispersive liquid–liquid microextraction followed by high‐performance liquid chromatography for the determination of fluoxetine in human plasma and urine samples was developed. The effects of six parameters on the extraction recovery were investigated and optimized utilizing Plackett–Burman design and Box–Benken design, respectively. According to the Plackett–Burman design results, the volume of disperser solvent, extraction time, and stirring speed had no effect on the recovery of fluoxetine. The optimized conditions included a mixture of 172 μL of 1‐octanol as extraction solvent and 400 μL of methanol as disperser solvent, pH of 11.3 and 0% w/v of salt in the sample solution. Replicating the experiment in optimized condition for five times, gave the average extraction recoveries equal to 90.15%. The detection limit of fluoxetine in human plasma was obtained 3 ng/mL, and the linearity was in the range of 10–1200 ng/mL. The corresponding values for human urine were 4.2 ng/mL with the linearity range from 10 to 2000 ng/mL. Relative standard deviations for intra and inter day extraction of fluoxetine were less than 7% in five measurements. The developed method was successfully applied for the determination of fluoxetine in human plasma and urine samples.  相似文献   

3.
A high‐throughput LC–MS/MS bioanalytical method was developed and validated for the determination of hydrocortisone in mouse serum via supported liquid extraction (SLE) in a 96‐well plate format. Although sample extracts from SLE result in similar matrix effects compared with conventional liquid–liquid extraction (LLE), greater analyte extraction recovery and much higher analysis throughput for the quantitative analysis of hydrocortisone in mouse serum were obtained. The current LC‐MS/MS method was validated for a concentration range of 2.00–2000 ng/mL for hydrocortisone using a 0.100 mL volume of mouse serum. The intra‐ and inter‐day precision and accuracy of the quality control samples at low, medium and high concentration levels showed ≤12.9% CV and ?3.4–6.2% bias for the analyte in mouse serum. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

4.
The present studies describe the systematic quality by design (QbD)‐oriented development and validation of a simple, rapid, sensitive and cost‐effective reversed‐phase HPLC bioanalytical method for nevirapine in rat plasma. Chromatographic separation was carried out on a C18 column using isocratic 68:9:23% v/v elution of methanol, acetonitrile and water (pH 3, adjusted by orthophosphoric acid) at a flow rate of 1.0 mL/min using UV detection at 230 nm. A Box–Behnken design was applied for chromatographic method optimization taking mobile phase ratio, pH and flow rate as the critical method parameters (CMPs) from screening studies. Peak area, retention time, theoretical plates and peak tailing were measured as the critical analytical attributes (CAAs). Further, the bioanalytical liquid–liquid extraction process was optimized using an optimal design by selecting extraction time, centrifugation speed and temperature as the CMPs for percentage recovery of nevirapine as the CAA. The search for an optimum chromatographic solution was conducted through numerical desirability function. Validation studies performed as per the US Food and Drug Administration requirements revealed results within the acceptance limit. In a nutshell, the studies successfully demonstrate the utility of analytical QbD approach for the rational development of a bioanalytical method with enhanced chromatographic separation and recovery of nevirapine in rat plasma. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

5.
A simple and sensitive method for the simultaneous determination of eight parabens in human plasma and urine samples was developed. The samples were preconcentrated using dispersive liquid–liquid microextraction based on the solidification of floating organic drops and determined by high‐performance liquid chromatography with ultraviolet detection. The influence of variables affecting the extraction efficiency was investigated and optimized using Placket–Burman design and Box–Behnken design. The optimized values were: 58 μL of 1‐decanol (as extraction solvent), 0.65 mL methanol (as disperser solvent), 1.5% w/v NaCl in 5.0 mL of sample solution, pH 10.6, and 4.0 min centrifugation at 4000 rpm. The extract was injected into the high‐performance liquid chromatography system for analysis. Under the optimum conditions, the linear ranges for eight parabens in plasma and urine were 1.0–1000 ng/mL, with correlation coefficients above 0.994. The limit of detection was 0.2–0.4 and 0.1–0.4 ng/mL for plasma and urine samples, respectively. Relative recoveries were between 80.3 and 110.7%, while relative standard deviations were less than 5.4%. Finally, the method was applied to analyze the parabens in 98 patients of primary breast cancer. Results showed that parabens existed widely, at least one paraben detected in 96.9% (95/98) of plasma samples and 98.0% (96/98) of urine samples.  相似文献   

6.
A highly sensitive and rapid bioanalytical method has been developed and validated for the estimation of indomethacin in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves a simple liquid–liquid extraction of indomethacin and phenacetin (internal standard, IS) from rat plasma with acetonitrile. Chromatographic separation was achieved with 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC18 column with a total run time 3.0 min. The MS/MS ion transitions monitored were 357.7 → 139.1 for indomethacin and 180.20 → 110.10 for IS. Method validation and pharmacokinetic study plasma analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.51 ng/mL and the linearity was observed from 0.51 to 25.5 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.00–10.2 and 5.88–9.80%, respectively. This novel method has been applied to an oral pharmacokinetic study in rats. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

7.
Chloropropanols are processing toxicants with a potential risk to human health due to the increased intake of processed foods. A rapid and efficient method for the determination of three chloropropanols in human plasma was developed using ultrasound‐assisted dispersive liquid–liquid microextraction. The method involved derivatization and extraction in one step followed by gas chromatography with tandem mass spectrometry analysis. Parameters affecting extraction, such as sample pH, ionic strength, type and volume of dispersive and extraction solvents were optimized by response surface methodology using a pentagonal design. The linear range of the method was 5–200 ng/mL for 1,3‐dichloro‐2‐propanol, 10–200 ng/mL for 2,3‐dichloro‐2‐propanol and 10–400 ng/mL for 3‐chloropropane‐1,2‐diol with the determination coefficients between 0.9989 and 0.9997. The limits of detection were in the range of 0.3–3.2 ng/mL. The precision varied from 1.9 to 10% relative standard deviation (n = 9). The recovery of the method was between 91 and 101%. Advantages such as low consumption of organic solvents and short time of analysis make the method suitable for the biomonitoring of chloropropanols.  相似文献   

8.
Boldine is a potential anti‐inflammatory agent found in several different plants. Published bioanalytical methods using HPLC with ultraviolet and fluorescent detection lacked enough sensitivity and required tedious sample preparation procedures. Herein, we describe the development of a novel ultra‐high performance LC with MS/MS for determination of boldine in plasma. Boldine in plasma was recovered by liquid–liquid extraction using 1 mL of methyl tert‐butyl ether. Chromatographic separation was performed on a C18 column at 45°C, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. The detection was performed on an electrospray triple‐quadrupole MS/MS by positive ion multiple reaction monitoring mode. Good linearity (r2 > 0.9926) was achieved in a concentration range of 2.555–2555 ng/mL with a lower limit of quantification of 2.555 ng/mL for boldine. The intra‐ and inter‐day precisions of the assay were 1.2–6.0 and 1.8–7.4% relative standard deviation with an accuracy of ?6.0–8.0% relative error. This newly developed method was successfully applied to a single low‐dose pharmacokinetic study in rats and was demonstrated to be simpler and more sensitive than the published methods, allowing boldine quantification in reduced plasma volume. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

9.
A rapid and novel method combining dispersive liquid–liquid microextraction and high-performance liquid chromatography coupled with fluorescence detection was developed for the determination of donepezil in human urine. Parameters affecting extraction efficiency and chromatographic determination, such as the type and volume of the extraction and disperser solvent, pH of sample for dispersive liquid–liquid microextraction, mobile-phase composition, pH, column oven temperature, and flow rate for chromatographic determination, were evaluated and optimized. Using a C18 core–shell column (7.5 × 4.6?mm, 2.7?μm), the determination of donepezil was accomplished within 5?min. Under optimum conditions, developed method was linear in the range of 0.5–25?ng?mL?1 with the correlation coefficient >0.99. Limit of detection was 0.15?ng?mL?1. The relative standard deviation at three concentration levels (2, 12.5, and 20?ng?mL?1) was less than 11% with accuracy in the range of 96.9–102.8%. The results of this study demonstrate that the use of dispersive liquid–liquid microextraction and core–shell column can be considered as a powerful tool for the analysis of donepezil in human urine.  相似文献   

10.
A novel, simple, specific, sensitive and reproducible high‐performance liquid chromatography assay method has been developed and validated for the estimation of Orteronel in rat plasma. The bioanalytical procedure involves extraction of Orteronel and phenacetin (internal standard) from rat plasma with a simple liquid–liquid extraction process. The chromatographic analysis was performed on a Waters Alliance system using a gradient mobile phase conditions at a flow rate of 1 mL/min and a C18 column maintained at ambient room temperature. The eluate was monitored using a photodiode array detector set at 242. Orteronel and internal standard eluted at 4.8 and 6.2 min, respectively and the total run time was 9 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 100–3149 ng/mL (r2 = 0.995). The intra‐ and inter‐day precisions were in the ranges of 0.31–7.87 and 3.97–6.35, respectively, in rat plasma. The validated HPLC method was successfully applied to a pharmacokinetic study of Orteronel in rats. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

11.
A simple and sensitive method for the extraction of four phthalate esters including dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl phthalate (BBP) and di-n-butyl phthalate (DBP) as well as their determination in water samples was developed using homogeneous liquid–liquid extraction (HLLE) and HPLC-UV. The extraction method is based on the phase separation phenomenon by the salt addition to the ternary solvent system. The extraction parameters such as type and volume of extracting and consolute solvent, concentration of salt, pH of sample and extraction time were optimized. Under the optimal conditions (extraction solvent: 100?µL CHCl3; consolute solvent: 2.0?mL methanol; NaCl 15% (w/v) and pH of sample: 6.5) extraction recovery was in the range of 92–102%. Linearity was observed in the range of 0.5–300?µg?L?1 for DEP and 0.6–300?µg?L?1 for DMP, BBP and DBP. Correlation coefficients (r 2), limits of detection (LODs) and relative standard deviations (RSDs) were in the ranges of 0.9976–0.9993, 0.18–0.25 and 1.5–4.8%, respectively. The method was successfully applied for the preconcentration and determination of these phthalate esters in the several environmental water samples.  相似文献   

12.
A rapid and simple method for the extraction and preconcentration of ceftazidime in aqueous samples has been developed using dispersive liquid–liquid microextraction followed by high‐performance liquid chromatography analysis. The extraction parameters, such as the volume of extraction solvent and disperser solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction time, and temperature in the dispersive liquid–liquid microextraction process, were studied and optimized with the experimental design methods. Firstly, for the preliminary screening of the parameters the taguchi design was used and then, the fractional factorial design was used for significant factors optimization. At the optimum conditions, the calibration curves for ceftazidime indicated good linearity over the range of 0.001–10 μg/mL with correlation coefficients higher than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water and urine samples, respectively. The proposed method successfully employed to determine ceftazidime in water and urine samples and good agreement between the experimental data and predictive values has been achieved.  相似文献   

13.
A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro‐aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25–1000 ng/mL for agomelatine; 0.25–100 ng/mL for asenapine and iloperidone; 2.5–1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3–924.6 ng/mL for dehydroaripiprazole; 2.2–878.4 ng/mL for melperone; and 2.2–883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra‐run precision of 0.4–5.5 %, inter‐run precision of 0.6–8.2% and overall recovery of 87.9–114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

14.
A simple, specific, sensitive and reproducible high‐performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of odanacatib in rat and human plasma. The bioanalytical procedure involves extraction of odanacatib and itraconazole (internal standard, IS) from a 200 μL plasma aliquot with simple liquid–liquid extraction process. Chromatographic separation was achieved on a Symmetry Shield RP18 using an isocratic mobile phase at a flow rate of 0.7 mL/min. The UV detection wave length was 268 nm. Odanacatib and IS eluted at 5.5 and 8.6 min, respectively with a total run time of 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 50.9–2037 ng/mL (r2 = 0.994). The intra‐ and inter‐day precisions were in the range of 2.06–5.11 and 5.84–13.1%, respectively, in rat plasma and 2.38–7.90 and 6.39–10.2%, respectively, in human plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

15.
A rapid, sensitive and specific LC‐MS/MS method was developed and validated for quantifying chlordesmethyldiazepam (CDDZ or delorazepam), the active metabolite of cloxazolam, in human plasma. In the analytical assay, bromazepam (internal standard) and CDDZ were extracted using a liquid‐liquid extraction (diethyl‐ether/hexane, 80/20, v/v) procedure. The LC‐MS/MS method on a RP‐C18 column had an overall run time of 5.0 min and was linear (1/x weighted) over the range 0.5–50 ng/mL (R > 0.999). The between‐run precision was 8.0% (1.5 ng/mL), 7.6% (9 ng/mL), 7.4% (40 ng/mL), and 10.9% at the low limit of quantification—LLOQ (0.500 ng/mL). The between‐run accuracies were 0.1, –1.5, –2.7 and 8.7% for the above mentioned concentrations, respectively. All current bioanalytical method validation requirements (FDA and ANVISA) were achieved and it was applied to the bioequivalence study (Cloxazolam—test, Eurofarma Lab. Ltda and Olcadil®— reference, Novartis Biociências S/A). The relative bioavailability between both formulations was assessed by calculating individual test/reference ratios for Cmax, AUClast and AUC0‐inf. The pharmacokinetic profiles indicated bioequivalence since all ratios were as proposed by FDA and ANVISA. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

16.
Pathak SM  Kumar AR  Musmade P  Udupa N 《Talanta》2008,76(2):338-346
A sensitive high performance liquid chromatographic (HPLC) method involving fluorescence detection was developed for the determination of fexofenadine (FEX), known to have low oral bioavailability, in rat plasma. In order to understand the effect of various chromatographic factors on the separation of analytes and to simultaneously optimize the resolution and analysis run time, a response surface method was used. The chromatographic separation was achieved using a Supelco C(18)-DB (250 mm x 4.6mm I.D./5 microm particle size) column with mobile phase comprising of ammonium acetate buffer and acetonitrile (63:37, v/v), delivered isocratically at a flow rate of 1.0 mL min(-1). Diphenhydramine was used as an internal standard (I.S.). The statistical evaluation of the method was examined and the method was found to be precise and accurate with a linearity range of 1-500 ng mL(-1) (r>0.9980). The intra- and inter-day precision studies showed good reproducibility with coefficients of variation (C.V.) less than 12.26%. The advantages of our method are small sample volume (100 microL), short time of analysis (13 min) and a simple sample extraction and clean-up as compared to the previously published methods. The established method provides a reliable bioanalytical methodology to carry out FEX pharmacokinetics in rat plasma.  相似文献   

17.
This study developed a facile, highly sensitive technique for extracting and quantifying barbiturates in serum samples. This method combined ultrasound and surfactant-assisted dispersive liquid–liquid microextraction with poly(ethylene oxide)-mediated stacking in capillary electrophoresis. Factors influencing the extraction and stacking performance, such as the type and volume of extraction solvents, the type and concentration of surfactant, extraction time, salt additives, sample matrix, solution pH, and composition of the background electrolyte, were carefully studied and optimized to achieve the optimal detection sensitivity. Under the optimized extraction (injecting 140 μL C2H4Cl2 into 1 mL of sample with pH 4 (5 mM sodium phosphate containing 0.05 mM Tween 20 and sonication for 1 min) and separation conditions (150 mM tris(hydroxymethyl)aminomethane-borate with pH 8.5 containing 0.5% (m/v) poly(ethylene oxide)), the limits of detection (signal-to-noise ratio = 3) of five barbiturates ranged from 0.20 to 0.33 ng/mL, and the calculated sensitivity improvement ranged from 868- to 1700-fold. The experimental results revealed excellent linearity (R2 > 0.99), with relative standard deviations of 2.1%–3.4% for the migration time and 4.3%–5.7% for the peak area. The recoveries of the spiked serum samples were 97.1% –110.3%. Our proposed approach offers a rapid and practical method for quantifying barbiturates in biological fluids.  相似文献   

18.
A high-throughput bioanalytical method for simultaneous quantitation of pravastatin and its metabolite (M1) in human serum was developed and validated using on-line extraction following liquid chromatography tandem mass spectrometry (LC-MS/MS). The on-line extraction was accomplished by the direct injection of a 50 microL serum sample, mixed 4:1 with an aqueous internal standard solution, into one of the extraction columns with aqueous 1 mm formic acid at flow rate of 3 mL/min. The separation and analysis were achieved by back-eluting the analytes from the extraction column and the analytical column to the mass spectrometer with an isocratic mobile phase consisting of 62% aqueous 1 mm formic acid and 38% acetonitrile at a flow rate of 0.8 mL/min. The second extraction column was being equilibrated while the first column was being used for analysis, and vice versa. The standard curve range was 0.500-100 ng/mL for pravastatin and M1. The lower limit of quantitation, 0.500 ng/mL for all the analytes, was achieved when 50 microL of human serum was used. The intra- and inter-day precisions were within 7.4%, and the accuracy was between 95 and 103%. The on-line extraction was finished in 0.5 min and total analysis time was 2.5 min per sample.  相似文献   

19.
A sensitive method based on ionic liquid for single‐drop liquid microextraction coupled with HPLC‐UV was developed for the determination of carbonyl compounds in environmental waters using 1‐octyl‐3‐methylimidazolium hexafluorophosphate [C8min][PF6] as extraction solvent and 2,4‐dinitrophenylhydrazine as derivatizing agent. The extraction parameters affecting the enrichment factors such as solvent volume, pH, extraction time and salt concentration were investigated. A homemade funnel form polytetrafluoroethylene sleeve was fixed at the tip of the syringe needle and this allowed the use of 10 μL drop of ionic liquid for direct immersion extraction. Under the optimal conditions, the remarkable enrichment factors up to 150‐fold were obtained depending on the target analytes. The method has been validated when rectilinear relationship was obtained between the concentrations of analytes and peak area in the range of 5–100 ng/mL, the correlation coefficients were from 0.995 to 0.998, and the limit of detection was in the range of 0.04–2.03 ng/mL. The method was applied to monitor the concentration of carbonyl compounds in environmental waters with spiked recovery in the range of 84.2–106.9%.  相似文献   

20.
In the present study, dispersive liquid-liquid microextraction (DLLME) using an ionic liquid (IL) as the extractant was successfully developed to extract four benzophenone-type UV filters from the different water matrices. Orthogonal array experimental design (OAD), based on five factors and four levels (L(16)(4(5))), was employed to optimize IL-dispersive liquid-liquid microextraction procedure. The five factors included pH of sample solution, the volume of IL and methanol addition, extraction time and the amount of salt added. The optimal extraction condition was as follows. Sample solution was at a pH of 2.63 in the presence of 60 mg/mL sodium chloride; 30 μL IL and 15 μL methanol were used as extractant and disperser solvent, respectively; extraction was achieved by vortexing for 4 min. Using high-performance liquid chromatography-UV analysis, the limits of detection of the target analytes ranged between 1.9 and 6.4 ng/mL. The linear ranges were between 10 or 20 ng/mL and 1000 ng/mL. This procedure afforded a convenient, fast and cost-saving operation with high extraction efficiency for the model analytes. Spiked waters from two rivers and one lake were examined by the developed method. For the swimming pool water, the standard addition method was employed to determine the actual concentrations of the UV filters.  相似文献   

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