Micellar liquid chromatographic method for the determination of ephedrine and pseudoephedrine in human serum by direct inject of the sample with simple dilution

A micellar high-performance liquid chromatographic method was developed to simultaneously determine ephedrine and pseudoephedrine in human serum. The serum sample pretreatment was a simple dilution in a micellar solution, filtration, and direct injection, thus avoiding time-consuming and tedious steps. Hence, there is no need to use an internal standard. The serum samples were analyzed using a mobile phase containing 1.50?×?10^?1?mol/L sodium dodecyl sulfate and 0.02?mol/L sodium dihydrogen phosphate with 7.5% (v/v) 1-propanol at pH 3.0, running at 1.0?mL/min by an Inertsil C18 (150?×?4.6?mm, 5?µm) column at 30°C. The UV wavelength was set at 210?nm. The developed method was validated by linearity (r?>?0.9990) and intra- and inter-day precisions of ephedrine and pseudoephedrine (relative standard deviation; RSD%, 0.04–10.40, and RSD %, 0.30–10.25, respectively), LODs for ephedrine and for pseudoephedrine was 2.63 and 2.70?µg/mL, respectively; lower limit of quantification for ephedrine and for pseudoephedrine was 4.38 and 4.51?µg/mL, respectively. Finally, the proposed method was applied to investigate ephedrine and pseudoephedrine in real human serum samples after oral administration of Kechuanning Koufye including Ephedra herb. It is environmentally friendly, easy-to-handle, and feasible method for routine analysis in clinical laboratory.     

Flow‐Injection Chemiluminescence Analysis of Cloperastione Hydrochloride

Abstract

A new chemiluminescence (CL) reaction was observed when cloperastine hydrochloride was injected into the reaction mixture after the CL reaction of Ce(IV) and sodium sulfite finished. A new flow injection CL method for the determination of cloperastine hydrochloride was established based on the CL reaction. The relative standard deviation (RSD) for the determination of cloperastine hydrochloride was 1.3% (n=11, c=1.0×10^?6 g/mL). The CL intensity responded linearly to the concentration of cloperastine hydrochloride in the range 2.0×10^?7～2.0×10^?5 g/mL (r=0.9962). The detection limit was 5×10^?8 g/mL cloperastine hydrochloride. The method had been applied to the determination of cloperastine hydrochloride in tablets with satisfactory results.     

Etilefrine Plastic Membrane Electrodes Based on Individual and Mixed Ion-exchangers of Etilefrinium Phosphotungstate and Tetraphenylborate.

Abstract

Etilefrine hydrochloride (EfCl) selective PVC membrane electrodes based on Etilefrinium phosphotungstate (I), Etilefrinium tetraphenylborate (II) and a mixture of both (III) were prepared, The electrodes exhibited near Nernstian response over the concentration ranges 5.0 × 10^?6 - 1.0 × 10^?1, 6.3 × 10^?6 - 1.0 × 10^?1 and 6.3 × 10^?5 - 1.0 × 10^?1 M EfCl for electrodes I, II and III, respectively. The working pH ranges of electrodes I, II and III were 10 - 8.0, 10 - 7.5 and 10 - 7.5 and their isothermal coefficients were 0.00150, 0.00088 and 0.00072 V/°C, respectively. The electrodes showed good selectivity to EfCl with respect to many inorganic cations, sugars and amino acids. The standard additions method was used to determine EfCl in pure solutions and in pharmaceutical preparations.     

LC–MS–MS Simultaneous Determination of Paracetamol, Pseudoephedrine and Chlorpheniramine in Human Plasma: Application to a Pharmacokinetic Study

A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method was developed for the simultaneous determination of paracetamol, pseudoephedrine and chlorpheniramine in human plasma. Diphenhydramine was used as the internal standard. Analytes were extracted from alkalized human plasma by liquid–liquid extraction (LLE) using ethyl acetate. After electrospray ionization positive ion fragments were detected in the selected reaction monitoring (SRM) mode with a triple quadrupole tandem mass spectrometer. The method was linear in the concentration range of 20.0–10000.0 ng mL^?1 for paracetamol, 1.0–500.0 ng mL^?1 for pseudoephedrine and 0.1–50.0 ng mL^?1 for chlorpheniramine. The intra- and inter-day precisions were below 14.5% and the bias was between ?7.3 and +2.8% for all analytes. The validated LC–MS–MS method was applied to a pharmacokinetic study in which each healthy Chinese volunteer received a tablet containing 300 mg benorylate, 30 mg pseudoephedrine hydrochloride and 2 mg chlorpheniramine maleate. This is the first assay method described for the simultaneous determination of paracetamol, pseudoephedrine and chlorpheniramine in human plasma samples.     

Construction and Validation of New Electrochemical Carbon Nanotubes Sensors for Determination of Acebutolol Hydrochloride in Pharmaceuticals and Biological Fluids

A simple, rapid and a highly selective method for direct electrochemical determination of acebutolol hydrochloride (AC) was developed. The developed method was based on the construction of three types of sensors conventional polymer (I), carbon paste (II) and modified carbon nanotubes (MCNTs) carbon paste (III). The fabricated sensors depend mainly on the incorporation of acebutolol hydrochloride with phosphotungstic acid (PTA) forming ion exchange acebutolol‐phosphotungstate (AC‐PT). The performance characteristics of the proposed sensors were studied. The sensors exhibited Nernstian responses (55.6 ± 0.5, 57.14 ± 0.2 and 58.6 ± 0.4 mV mol L^?1) at 25 °C over drug concentration ranges (1.0 × 10^?6‐1.0 × 10^?2, 1.0 × 10^?7‐1.0 × 10^?2 and 5.0 × 10^?8‐1.0 × 10^?2 mol L^?1 with lower detection limits of (5.0 × 10^?7, 5.0 × 10^?8 and 2.5 × 10^?8 mol L^?1 for sensors (I), (II) and (III), respectively. The influence of common and possible interfering species, pharmaceutical additives and some related pharmacological action drugs was investigated using separate solution method and no interference was found. The stability indicating using forced degradation of acebutolol hydrochloride was studied. The standard addition method was used for determination of the investigated drug in its pharmaceutical dosage forms and biological fluids. The results were validated and statistically analysed and compared with those from previously reported methods.     

Post‐chemiluminescence Method of the Determination of Loperamide Hydrochloride in Human Plasma and Pharmaceutical by Using Dichlorofluorescein as Chemiluminescence Reagent

Abstract

A post‐chemiluminescence (PCL) was observed when loperamide hydrochloride solution was injected into the reaction mixture after the finish of CL reaction of alkaline N‐Chlorosuccinimide (NCS) and dichlorofluorescein. Based on this phenomenon, a simple, sensitive and fast flow injection PCL method was established for the determination of loperamide hydrochloride. The possible mechanism for the PCL reaction was discussed via the investigation of the CL kinetic characteristics, the CL spectra, the fluorescence spectra. The PCL intensity responded linearly to the concentration of loperamide hydrochloride in the range 8.0×10^?10 to 6.0×10^?7 g · ml^?1 with a linear correlation of 0.9995. The detection limit was 4×10^?10 g · ml^?1. The relative standard deviation was 2.4% for 4.0×10^?8 g · ml^?1 loperamide hydrochloride (n=11). This method has been applied to the determination of loperamide hydrochloride in human plasma and pharmaceutical samples with satisfactory results.     

Evaluation and Application of the Internal Standard Technique for the Direct Determination of Copper in Fruit Juices Employing Fast Sequential Flame Atomic Absorption Spectrometry

Abstract

The present paper describes the evaluation and application of internal standard for the determination of copper in fruit juices, employing Fast Sequential Flame Atomic Absorption Spectrometry (FS FAAS). The internal standards tested were indium, cobalt, and nickel using correlation graphs. However, indium was used, considering the composition of the samples. After this step, copper was determined in fruit juices using indium as internal standard. This method allows the determination of copper with a limit of quantification of 0.011 mg L^?1. The fruit juice samples selected for analysis were of grape, orange, pineapple, peach, cashew, and strawberry. The contents of copper in these samples varied from 0.02 to 0.42 mg L^?1. The analytical results were compared with the results obtained by analysis of these samples after complete mineralization using acid digestion and determination employing FS FAAS. The statistical comparison by a t-test (95% confidence level) showed no significant difference between the results. The relative standard deviations (RSD) with and without the use of the internal standard for a copper solution containing 0.4 mg L^?1 were of 0.62 and 1.94%, respectively. The use of indium as internal standard provided more accurate analytical results, as well as better analytical performance for the determination of copper in juice samples.     

Stability-Indicating High Performance liquid Chromatographic Determination of Diltiazem Hydrochloride

Abstract

A rapid, selective and accurate high-performance liquid chromatography method (HPLC) for the determination of diltiazem hydrochloride using clonazepam as internal standard is developed. The investigated compounds were eluted from 5 u Micropak MCH-5 reversed phase column at ambient temperature with a mobile phase comprising of acetonitrile-water (48:52%) at pH 3.3 and containing 0. 01M sodium-n-octane sulfonate as an ion pairing substance. The mobile phase was pumped at a flow rate of 1 ml min^?1 and the effluent was monitored at 239 nm. The retention times of the internal standard and diltiazem were at 3 min and 9 min, respectively. A linear relationship was derived between the peak height ratio (diltiazem/clonazepam) and diltiazem concentration over the range 1–10 μg ml^?1. Detection limit for the drug is 0.2 μg ml^?1 at 0.01 aufs. The developed procedure was applied to study the stability of diltiazem in the presence of its degradation products as well as in the presence of formulation excipients.     

Papaverine-Selective Plastic Membrane Electrode Based on Papaverinium Tetraphenylborate

Abstract

A plasticized PVC membrane containing the lipophilic salt papaverinium-tetraphenylborate was used to construct an ion-selective electrode for papaverine hydrochloride (Pv⁺Cl^?). The electrode shows near Nernstian response over the concentration range 1.6 × 10^?5 1.3C × 10^?2M PvCl in solutions of pH 1.0–6.2 at 25[ddot]C. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. The electrode showed very good selectivity for Pv with respect to a large number of inorganic and organic cations. The potentiometric titration and standard addition methods were used to determine Pv in pure solutions and in pharmaceutical preparations.     

Simultaneous Quantitation of Paracetamol, Pseudoephedrine and Chlorpheniramine in Dog Plasma by LC-MS-MS

A simple, rapid and sensitive liquid chromatography/electrospray tandem mass spectrometry quantitative detection method, using amantadine as internal standard, was developed for the simultaneous analysis of paracetamol, pseudoephedrine and chlorpheniramine concentrations. Analytes were extracted from plasma samples by liquid–liquid extraction with n-hexane–dichloromethane–2-propanol (2:1:0.1, v/v), separated on a C18 reversed-phase column with 0.1% formic acid–methanol (40:60, v/v) and detected by electrospray ionization mass spectrometry in positive multiple reaction monitoring mode. Calibration curves for plasma were linear over the concentration range 10–10,000 ng mL^?1 of paracetamol, 2–2,000 ng mL^?1 of pseudoephedrine and 0.2–200 ng mL^?1 of chlorpheniramine. The method has a lower limit of quantitation of 10 ng mL^?1 for paracetamol, 2.0 ng mL^?1 for pseudoephedrine and 0.2 ng mL^?1 for chlorpheniramine. Recoveries, precision and accuracy results indicate that the method was reliable within the analytical range, and the use of the internal standard was very effective for reproducibility by LC-MS-MS. This method is feasible for the evaluation of pharmacokinetic profiles of a novel multicomponent sustained release formulation containing 325 mg of paracetamol, 30 mg of pseudoephedrine hydrochloride and 2 mg of chlorpheniramine maleate. It is the first time the pharmacokinetic evaluation of a novel sustained-action formulation containing paracetamol, pseudoephedrine and chlorpheniramine has been elucidated in vivo using LC-MS-MS.     

Determination of Three Imidazole Derivatives by Flow-Injection Chemiluminescence

Abstract

A rapid, simple, and sensitive method was developed for the determination of three imidazole derivatives based on their quenching effect on bis(2,4,6-tricholorophenyl) oxalate (TCPO)–H₂O₂ chemiluminescence (CL) in the presence of rhodamine 6 G. Conditions affecting CL intensity were studied. With sodium dodecyl sulfate (SDS) as the additional agent, the relative standard deviation (RSD) was more twice the RSD without SDS. Under optimal conditions, good linear ranges were obtained from 1.0 × 10^?4 g/mL to 1.0 × 10^?6 g/mL, 1.0 × 10^?5 g/mL to 1.0 × 10^?7 g/mL, and 1.0 × 10^?5 g/mL to 7.0 × 10^?7 g/mL, with detection limits of 8.0 × 10^?7 g/mL, 7.0 × 10^?8 g/mL, and 8.0 × 10^?8 g/mL (S/N = 3) for hydrobenzole hydrochloride, thiamazole, and mizolastine, respectively. The RSDs for 13 consecutive injections of 1.0 × 10^?6 g/mL hydrobenzole hydrochloride, thiamazole, and mizolastine were 1.89%, 1.47%, and 1.69%, respectively, and satisfied results were obtained with the method applied to their pharmaceutical preparations. The possible CL mechanism was simply discussed.     

Green Spectrophotometric Method for the Quantitative Analysis of Vancomycin in Pharmaceuticals and Comparison with HPLC

Abstract

A spectrophotometric method for the determination of vancomycin base, (VCM), and vancomycin hydrochloride, (HVCM), based on the reaction with copper (II) ions, is presented. The obtained detection limit is about 4.5×10^?5 mol L^?1. The working analytical range falls between 1.0×10^?3 mol L^?1 and 1.0×10^?2 mol L^?1. Recovery studies in presence of excipients were performed. The recovery results were compared with HPLC. For HVCM the proposed method presented similar recovery to that of HPLC, 100.4% vs. 100.2%, but better precision, 1.9% vs. 6.1%. In the VCM case the recovery is quite better, 100.5% vs. 89.6%, with a little smaller precision, 2.1% vs. 1.3%.     

Electrogenerated Chemiluminescence (ECL) Determination of Ephedrine with a Self-Assembly Multilayer Ni(II)-Polyluminol Modified Electrode

By combining the layer-by-layer (LBL) self-assembly technique with the electrochemical polymerization method, multilayer Ni(II)-polyluminol films were modified on the surface of a vaseline-impregnated graphite electrode. It was found that, compared with an electrode modified by direct electrochemical polymerization, this modified electrode offered a suitable ECL reaction micro-environment created by the special multilayer films, which was beneficial to the ephedrine hydrochloride enhancing effect for luminol ECL intensity. The ECL enhancing effect of ephedrine hydrochloride on the electro-oxidation luminol was improved on this modified electrode. Based on this finding, a new sensitive ECL method was developed for ephedrine hydrochloride determination under the optimal conditions. At the same time, a new idea is proposed for improving the analytical performance of the luminol ECL system by modifying the ECL reaction micro-environment with the layer-by-layer self- assembly method. Under the optimum experimental conditions, the ephedrine hydrochloride concentration in the range of 2.0 × 10⁻⁸–7.0 × 10⁻⁶ mol L⁻¹ was proportional to the enhanced ECL signal, and it offered an 8.0 × 10⁻⁹ mol L⁻¹ detection limit for ephedrine hydrochloride.     

Electrochemical applications and computational studies on ephedrine drug

A novel, simple, sensitive and highly selective pseudo-carbon paste electrode modified with poly(acrylic) acid (PCPE-PAA) was described to be useful for the electrochemical determination of ephedrine substance. The PCPE-PAA electrode was characterized using scanning electron microscope (SEM) and cyclic voltammetry. Cyclic voltammogram for ephedrine shows only one anodic oxidation peak at 1.15?V (vs. SCE) using Britton–Robinson buffer (pH 9). Theoretical calculations were performed using PM3 method to be helpful in studying the electrochemical behavior of ephedrine. The highest occupied orbitals (HOMO) of ephedrine and the lowest unoccupied orbitals (LUMOs) of its oxidation product (methcathinone) are mainly localized in the side chain of benzene ring. The values of HOMOs, LUMOs and atomic charges clearly indicate that the oxidation process occurs on the hydroxyl group of ephedrine forming ketone group, supporting the proposed electrochemical mechanism. Square wave voltammetry was used for the direct electrochemical determination of ephedrine. Ephedrine gives a linear range from 6?×?10^?5 to 1?×?10^?3?M with a correlation coefficient of 0.998 and a relative standard deviation of 2.165?×?10^?7. A lower detection limit of 3.5?×?10^?7?M was obtained. The effect of some interferences such as ascorbic acid, uric acid, urea, glucose and glycine on the peak height of ephedrine was examined. The suggested method has been applied successfully for the direct electrochemical determination of ephedrine in urine and different pharmaceutical formulations.     

Simultaneous Determination of Dipyrone and Papaverine in Pharmaceutical Formulation using PLS Regression and UV Spectrophotometry

Abstract

A combination of sodium dipyrone and papaverine hydrochloride is used as an analgesic and antispasmodic drug. A simple and rapid procedure is proposed for simultaneous determination of these drugs in commercial formulations (Melpaz^®) based on partial least squares (PLS) regression and UV spectrophotometric measurements in the range of 218–300 nm. The calibration set was built with 25 solutions in concentrations ranging from 15.0–35.0 mg ml^?1 for dipyrone and from 0.5–1.5 mg ml^?1 for papaverine in methanol. The relative standard deviation (RSD) was 1.05% for dipyrone and 1.55% for papaverine in pharmaceutical formulations. The percent of relative recovery was 95.9% for dipyrone and 95.2% for papaverine. Figures of merit, such as accuracy, precision, sensitivity and adjust were also determined. The methodology was validated by using an independent method, based on high performance liquid chromatography (HPLC).     

Micellar‐Enhanced Spectrofluorimetric Determination of Trazodone Hydrochloride in Human Urine and Serum

Abstract

A novel developed spectrofluorimetric method for the determination of trazodone hydrochloride in the presence of sodium dodecyl sulfate (SDS) surfactant micelles was described. Under optimal conditions, there was a good linear relationship between fluorescence intensity and trazodone hydrochloride concentration in the range of 4.0×10^?9 to 8.0×10^?6 mol · l^?1with the detection limit of 1.3×10^?9 mol · l^?1 (S/N=3). This method has been used to determine trazodone hydrochloride in biological fluids.     

Amperometric Determination of Bilirubin with Flow Injection Analysis System

Abstract

The amperometric method using the flow injection system has been developed for the determination of bilirubin. Bilirubin is oxidized to biliverdin at the glassy carbon working electrode. The optimum conditions were investigated. Linear calibration curve was obtained between 1.0×10⁶ and 1.0×10^?3M, with a sampling rate of 20 samples h^?1 and a relative standard deviation of 3.2%. The limit of detection is 4.0×10^?7M. Interference of hemoglobin was not observed.     

Flow Injection Chemiluminescence Determination of Difenidol Hydrochloride Using N-Chlorosuccinimide-Dichlorofluorescein Reaction

Abstract

A flow injection method combined with chemiluminescence detection was described for the determination of difenidol hydrochloride. Strong chemiluminescence was recorded when difenidol hydrochloride was added into the reaction mixture of N-chlorosuccinimide with dichlorofluorescein in alkaline medium. The experimental conditions that affected the chemiluminescence signal, including the concentrations of reactants, the reaction medium, and the instrumental parameters, were carefully optimized. Under the optimum experimental conditions, the enhanced chemiluminescence intensity was linear related to the concentration of difenidol hydrochloride in the range of 4.0 × 10^?9 to 4.0 × 10^?7 g/ml. The detection limit for difenidol hydrochloride was 7 × 10^?10 g/ml, and the sample throughput was 90/h. The relative standard deviation was 2.5% for 5.0 × 10^?8 g/ml difenidol hydrochloride solution (n = 11). The interference of common inorganic ions, excipients, and additives used in pharmaceutical preparation was studied, which showed the method has higher tolerance limit for these substances and has good selectivity. As a preliminary application, the method was applied to the determination of difenidol hydrochloride in tablets, and the satisfactory results were achieved.     

Determination of Pseudoephedrine Hydrochloride in Some Pharmaceutical Drugs by Potentiometric Membrane Sensor Based on Pseudoephedrine–Phosphotungstate Ion Pair

Abstract

An ion-selective electrode (ISE) was developed for the rapid determination of pseudoephedrine hydrochloride (PSEHCl) in pharmaceutical preparations. The electrode incorporates a PVC membrane with a pseudoephedrine–phosphotungstate ion pair complex. The influences of membrane composition, temperature, pH of the test solution, and the interfering ions on the electrode performance were investigated. The sensor exhibits a Nernstian response for pseudoephedrine hydrochloride ions over a relatively wide concentration range (1.0 × 10^?1 to 1.0 × 10^?5 mol L^?1) with a slope of 56.2 ± 0.5 mV per decade at 25°C. It can be used in the pH range 4.0–10.5. The isothermal temperature coefficient of this electrode amounted to 0.0009 V/°C. The membrane sensor was successfully applied to determination of PSEHCl in its tablets and syrup.     

UPLC-ESI-MS-MS Determination of Three β2-Agonists in Pork

The chromatographic behaviour of bupropion hydrochloride, a basic drug of pK _a 7.9, has been investigated under reversed-phase ion-pairing conditions and the results were used to develop a method for analysis of bupropion hydrochloride in pharmaceuticals. Chromatographic separation of bupropion hydrochloride and carbamazepine (used as internal standard) was performed on a C₈ column (150 mm × 4.6 mm i.d., 3.5-μm particle), with 40:10:50 (v/v) methanol–acetonitrile–phosphate buffer (20 mm, pH 3.0), containing 10 mm 1-heptane sulfonic acid sodium salt (1-HSA), as optimum mobile phase at a flow rate of 1.0 mL min^?1. UV detection was at 254 nm. The fully validated method enables reproducible and selective analysis of bupropion hydrochloride in pharmaceuticals.