Continuous production of (S)-1-phenylethanol by immobilized cells of Rhodotorula glutinis with a specially designed process

A specially designed process for the continuous production of a chiral alcohol by immobilized Rhodotorula glutinis was prepared and is reported. The performance of the process with immobilized cells was also investigated. The run time of the immobilized cells, the flow rates of the substrate, and tris buffer containing 4% glucose in the process were optimized. The immobilized R. glutinis biocatalyst could be used for 15 days with maximum reaction activity. Under the optimized conditions, the continuous production process was operated for 30 days and resulted in 10.8 mL (S)-1-phenylethanol [(S)-1-PE]. The process has been demonstrated on a multigram scale in 75% overall yield with a purity of >99%.     

A Sensitive and Selective RP-LC Method for the Simultaneous Determination of the Antihypertensive Drugs,Enalapril, Lercanidipine,Nitrendipine and Their Validation

A RP-LC method is presented, which is sensitive and selective for the simultaneous determination of enalapril–lercanidipine and enalapril–nitrendipine binary mixtures in their pharmaceutical dosage forms. The analyte peaks were detected using the LC method with the mobile phase ratio of methanol: water (70:30 v/v, pH 3.0) and a 1.0 mL min⁻¹ flow rate. The detection wavelength was selected at 210 nm using photo diode array detector and column temperature was optimized to 30 °C. Linearity was obtained at different concentration ranges for all working pharmaceutically active compounds between 0.5 and 25 μg mL⁻¹. The proposed methods were extensively validated according to USP 27 requirements and ICH guidelines. The methods were applied to the analysis of pharmaceutical dosage forms containing binary mixtures of enalapril–lercanidipine and enalapril–nitrendipine. Moreover, the proposed methods were applied for the degradation studies of the selected compounds. Degradation studies were conducted using stress conditions such as UV light, acidic and alkaline hydrolysis, oxidation and heat in oven, to evaluate the ability of the separation of the response of standard compounds from their degradation products.

     

Simultaneous Determination and Drug Dissolution Testing of Combined Amlodipine Tablet Formulations Using RP-LC

In the proposed work, the simultaneous analysis of amlodipine–rosuvastatin and amlodipine–atorvastatin in their dosage forms was achieved. Simultaneous dissolution profiles of the amlodipine–rosuvastatin and amlodipine–atorvastatin tablets are realized using Apparatus II with a simple, accurate and precise RP-LC method. The mobile phase consisting of 0.2 % H₃PO₄ and pH 5:methanol:acetonitrile (46:27:27) was used. The samples of 10 µL were injected onto a Zorbax SB C18 (100 mm, 4.6 mm, 3.5 µm particle size) column with 1.2 µL min⁻¹ flow rate. The samples were detected at 236 nm. By plotting peak area ratios vs. concentration, the linearity for amlodipine–rosuvastatin and amlodipine–atorvastatin was determined. With the developed RP-LC method, AML, ROS and ATOR were detected within the range of 0.25–10, 0.5–10 and 0.25–25 µg mL⁻¹, respectively. LOD and LOQ values were also calculated as 0.028, 0.058, 0.021 and 0.095 µg mL⁻¹, 0.195 µg mL⁻¹, 0.070 µg mL⁻¹ for AML, ROS and ATOR, respectively. System suitability tests parameters, such as capacity factor, selectivity to previous peak, selectivity to next peak, resolution to previous peak, resolution to next peak, tailing factor, theoretical number of plates, were performed and found coherent with the ICH guideline parameters. The proposed method has been extensively validated in terms of recovery, and recovery results were between 99 and 101 %. For proving the precision, between-day and within-day repeatability results of the method were proposed. The method can be used for the simultaneous determination of amlodipine–rosuvastatin and amlodipine–atorvastatin.

     

Electrochemical Investigations of the Anticancer Drug Idarubicin Using Multiwalled Carbon Nanotubes Modified Glassy Carbon and Pyrolytic Graphite Electrodes

The effect of surface modifications on the electrochemical behavior of the anticancer drug idarubicin was studied at multiwalled carbon nanotubes modified glassy carbon and edge plane pyrolytic graphite electrodes. The surface morphology of the modified electrodes was characterized by scanning electron microscopy. The modified electrodes were constructed for the determination of idarubicin using adsorptive stripping differential pulse voltammetry. The experimental parameters such as supporting electrolyte, pH, accumulation time and potential, amount of carbon nanotubes for the sensitive assay of idarubicin were studied as details. Under the optimized conditions, idarubicin gave a linear response in the range 9.36×10^?8–1.87×10^?6 M for modified glassy carbon and 9.36×10^?8–9.36×10^?7 M for modified edge plane pyrolytic graphite electrodes. The detection limits were found as 1.87×10^?8 M and 3.75×10^?8 M based on modified glassy carbon and edge plane pyrolytic graphite electrodes, respectively. Interfering species such as ascorbic acid, dopamine, and aspirin showed no interference with the selective determination of idarubicin. The analyzing method was fully validated and successfully applied for the determination of idarubicin in its pharmaceutical dosage form. The possible oxidation mechanism of idarubicin was also discussed. The results revealed that the modified electrodes showed an obvious electrocatalytic activity toward the oxidation of idarubicin by a remarkable enhancement in the current response compared with bare electrodes.     

Erratum to: UPLC versus HPLC on Drug Analysis: Advantageous,Applications and Their Validation Parameters

Liquid chromatography (LC) is a separation technique used in many different areas to aid the identification and quantification of substances in various matrices. LC techniques with various detection modes have been widely used for the sensitive and selective determination of trace amounts of pharmaceutical active compounds in biological samples and their dosage forms. A completely new system design with advanced technology has been developed, called ultra high performance liquid chromatography, which has evolved from high performance liquid chromatography. The application of LC methods to drug analysis introduces a powerful tool for therapeutic drug monitoring as well as for clinical research. The advantages of short turnaround time, method reliability, method sensitivity, and drug specificity justify the use of LC techniques for various groups of the drug active compounds. This review describes some of the principles of ultra high performance liquid chromatography and high performance liquid chromatography, validation of these methods, system suitability tests for the methods, and application of methods to pharmaceutical analysis in the last 3 years.

     

UPLC versus HPLC on Drug Analysis: Advantageous, Applications and Their Validation Parameters

Liquid chromatography (LC) is a separation technique used in many different areas to aid the identification and quantification of substances in various matrices. LC techniques with various detection modes have been widely used for the sensitive and selective determination of trace amounts of pharmaceutical active compounds in biological samples and their dosage forms. A completely new system design with advanced technology has been developed, called ultra high performance liquid chromatography, which has evolved from high performance liquid chromatography. The application of LC methods to drug analysis introduces a powerful tool for therapeutic drug monitoring as well as for clinical research. The advantages of short turnaround time, method reliability, method sensitivity, and drug specificity justify the use of LC techniques for various groups of the drug active compounds. This review describes some of the principles of ultra high performance liquid chromatography and high performance liquid chromatography, validation of these methods, system suitability tests for the methods, and application of methods to pharmaceutical analysis in the last 3 years.     

Total production of (R)-3,5-bistrifluoromethylphenyl ethanol by asymmetric reduction of 3,5-bis(trifluoromethyl)-acetophenone in the submerged culture of Penicillium expansum isolate

A total of 82 fungal isolates were screened for their ability to reduce 3,5-bis(trifluoromethyl)-acetophenone 1. Penicillium expansum was found to successfully reduce ketone 1 in the submerged culture. A second screening was performed on the active P. expansum strains identified by the first screening. A number of strains of P. expansum were found to produce (R)-3,5-bistrifluoromethylphenyl ethanol 2 with over 99% enantiomeric excess (ee) from ketone 1. The most productive strain was identified as P. expansum EBK-9, and this strain was selected for further experiments. The total production of 2 was carried out by P. expansum EBK-9 in a laboratory-scale bioreactor employing optimized conditions as determined by our experiments. P. expansum EBK-9 gave 2 with ee >99% and 76% yield. On a large scale, a total of 3.35 g/L of 2 was produced from 1 after 56 h.     

Simultaneous determination and validation of some binary mixtures of antihypertensive drugs using ratio derivative spectrophotometric method

Ratio derivative spectrophotometric technique is presented for the rapid, accurate and precise simultaneous determination of olmesartan medoxomil (OLM), hydrochlorothiazide (HCT), and zofenopril (ZOF) as well as HCT binary mixtures in their dosage forms. First derivative of the ratio spectra (DD1) by measurements using different amplitudes was used and calibration graphs were established for 0.5–12 mg/mL HCT and 0.5–20 mg/mL OLM and ZOF. This method depends on first derivative of the ratio spectra by division of the absorption spectrum of the binary mixture by a standard spectrum of one of the components and then calculating the first derivative of the ratio spectrum. The first derivative of the ratio amplitudes at 250.4 and 291.5 nm for OLM, 250.4 and 298.1 nm for ZOF and 231.8, 332.2, 232.3 and 280.4 nm for HCT were selected for the determination. The proposed methods were successfully applied for determining of both drug combinations (ZOF-HCT and OLM-HCT) in their synthetic mixtures and in pharmaceutical dosage forms. The described procedures are extensively validated, non-destructive and do not require any separation steps.     

Stability-Indicating UPLC Method for the Determination of Bisoprolol Fumarate and Hydrochlorothiazide: Application to Dosage Forms and Biological Sample

A sensitive, selective and accurate ultra performance liquid chromatographic method has been developed and validated for the simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in their combined dosage forms and as well as in spiked human urine samples. The separation was achieved on an Acquity UPLC BEH C18 1.7 μm (2.1 × 50 mm) column, at 40 °C with mobile phase consisting of acetonitrile:phosphate buffer (20 mM) at pH 3.0 with a gradient elution at 225 nm. Bisoprolol fumarate and hydrochlorothiazide were well separated in <1.5 min with good resolution and without any tailing and interference of excipients. The method was fully validated according to ICH guidelines in terms of accuracy, precision, linearity and specificity. A linear response was observed over the concentration range 0.5–150 μg mL^?1 for hydrochlorothiazide and 0.5–250 μg mL^?1 for bisoprolol fumarate. Limit of detection and limit of quantitation for hydrochlorothiazide were calculated as 0.01 and 0.03 μg mL^?1, respectively, and for bisoprolol fumarate were 0.07 and 0.21 μg mL^?1, respectively. Moreover, bisoprolol fumarate and hydrochlorothiazide were subjected to degradation conditions such as hydrolytic, oxidative and thermal stress conditions to evaluate the ability of the proposed method for the separation of bisoprolol fumarate and hydrochlorothiazide from their degradation compounds.     

LC–MS Method for the Sensitive Determination of Metoclopramide: Application to Rabbit Plasma, Gel Formulations and Pharmaceuticals

To support real biological sample application, a simple, selective and rapid LC–MS method has been developed and validated for the sensitive determination of metoclopramide in rabbit blood, ex vivo permeation studies and pharmaceutical dosage form. LC–MS analysis was performed isocratically on a Zorbax SB-C₁₈ column with a mobile phase consisting of methanol:ammonium acetate buffer (pH 3.0) 75:25 (v/v) at a flow rate of 0.70 mL min^?1. The outlet of the column was connected to a single quadrupole mass spectrometer with positive mass spectrometric detection. Ions were detected in the positive multiple reaction monitoring mode. The assay was linear over the concentration range of 1.25–200 pg μL^?1 with a limit of detection of 0.077 pg μL^?1 for standard solutions and 2.5–200 pg μL^?1 with a limit of detection of 0.42 pg μL^?1 for serum samples. The method is applicable, covering a variety of pharmaceutical and biological studies. Metoclopramide was extracted from rabbit blood by liquid–liquid extraction using ether as the extraction solvent. The reproducibility of the method was found to be between 0.96 and 1.98 % (RSD) values. The proposed method has been extensively validated for the determination of metoclopramide in all working media. The sample preparations, flow rate and run time of the analytical systems are not time consuming. Moreover, for the stability of metoclopramide, the effect of temperature, UV light, H₂O₂, HCl and NaOH were also investigated.