Current Pharmaceutical Analysis - Volume 16, Issue 4, 2020

Antibiotics are an important class among drugs because they are a significant agent to deal with infections. Cephalosporins are a very important group of antibiotics in the β-lactam class. The cephalosporins are semisynthetic antibiotics derived from products of the fungus Cephalosporium. Cephalosporins are classified as first, second, third, fourth, and advanced generation, based largely on their antibacterial spectrum and stability to β-lactamases. Electrochemical methods have been used for the determination of cephalosporin just as used in the determination of many antibiotic drugs. Electroanalytical methods present generally high sensitivity, low cost, low requirements, ease of preparation of the samples in a very short time, and a short analysis time. The most commonly used types are cyclic voltammetry, differential pulse voltammetry, square wave voltammetry and linear sweep voltammetry. The aim of this review is to evaluate the advantages and uses of electroanalytical methods used in the determination of cephalosporins. In addition, current applications of the methods to the pharmaceutical analysis of cephalosporins will also be summarized in a table.

Background: The molecular imprinting technique has been applied in many fields including separation, artificial antibody mimics, catalysis, sensing studies, and drug delivery. The reasons for the popularity of this technique among the researchers are high selectivity due to the cavities that are formed on the polymer surface for the specific analyte, high robustness, high durability under extreme conditions and low cost. When these advantages are combined with the advantages of electrochemical methods such as rapid response time, ease of use, cheapness and miniaturizability, Molecularly Imprinted Polymer (MIP) based electrochemical sensors turn out to be a widely-preferred sensing tool. Objective: This article provides the reader with information on MIP-based electrochemical sensors and reviews the applications of the MIP sensors prepared by electropolymerization of orthophenylenediamine, a monomer whose mechanical and chemical stability is very high. Results and Conclusion: The literature survey summarized in this review shows that cyclic voltammetry is the most widely preferred electrochemical technique for electropolymerization of o-PD. The media chosen is generally acetate or phosphate buffers with different pH values. Although there are numerous solvents used for template removal, generally methanol and NaOH have been chosen.

Background: This review investigates the ophthalmic drugs that have been studied with voltammetry in the web of science database in the last 10 years. Introduction: Ophthalmic drugs are used in the diagnosis, evaluation and treatment of various ophthalmological diseases and conditions. A significant literature has emerged in recent years that investigates determination of these active compounds via electroanalytical methods, particularly voltammetry. Low cost, rapid determination, high availability, efficient sensitivity and simple application make voltammetry one of the most used methods for determining various kinds of drugs including ophthalmic ones. Methods: In this particular review, we searched the literature via the web of science database for ophthalmic drugs which are investigated with voltammetric techniques using the keywords of voltammetry, electrochemistry, determination and electroanalytical methods. Results: We found 33 types of pharmaceuticals in nearly 140 articles. We grouped them clinically into seven major groups as antibiotics, antivirals, non-steroidal anti-inflammatory drugs, anti-glaucomatous drugs, steroidal drugs, local anesthetics and miscellaneous. Voltammetric techniques, electrodes, optimum pHs, peak potentials, limit of detection values, limit of quantification values, linearity ranges, sample type and interference effects were compared. Conclusion: Ophthalmic drugs are widely used in the clinic and it is important to determine trace amounts of these species analytically. Voltammetry is a preferred method for its ease of use, high sensitivity, low cost, and high availability for the determination of ophthalmic drugs as well as many other medical drugs. The low limits of detection values indicate that voltammetry is quite sufficient for determining ophthalmic drugs in many media such as human serum, urine and ophthalmic eye drops.

Inductively coupled plasma is a new technique employed for the determination of elemental impurities in pharmaceutical ingredients viz. raw materials, drug substance, and drug product dosage forms. New US FDA and EMA regulations came into effect from Jan 2018 as industry standard requirements for the determination of inorganic elemental impurities using ICP-OES/AES or ICP-MS analytical techniques. The method development was optimized for the determination of the listed elements as per USP <232> <233> elemental impurities-limits and procedures. It also demonstrates the validation of the method and verification/transfer of the method which also provides an insight into the presence of free elemental atomics of the gaseous form of the sample (drug substance, drug product or excipients), thus helping in determining the concentration of the element of interest. Also, the regulatory guidance is very general and does not explain the sample specifications for the individual element concentrations. Thus, this review emphasizes the routine instrumental maintenance, analytical method development challenges, trends in the performance of analytical method validation and verification/ transfer activities of the various pharmaceutical dosage forms outlined with acceptance criterion.

Aim: A new simple and sensitive high-Performance Liquid Chromatography (HPLC) method for the determination of a potent synthetic cannabinoid THJ-2201, has been developed and validated. Lixiviptan was used as the Internal Standard (IS). Methods: THJ-2201 and IS were extracted from mouse plasma using deproteinization procedure that uses acetonitrile followed by HPLC analysis. The separation was carried out on a reversed-phase C18 column using water and acetonitrile mixture (30:70 v/v). The flow-rate was 1.0 mL/min. Eluting of both THJ-2201 and lixivaptan was performed at 220 nm. Results: The method demonstrated linearity over a calibration range of 95 - 1500 ng/mL and the Limit of Detection (LOD) and Quantitation (LOQ) were 28 ng/mL and 91 ng/mL, respectively. The validation of the proposed method was carried out by following the US Food and Drug Administration (FDA) guidelines. Intra- and inter-day precision did not exceed 6.4%, whereas the accuracy of THJ-2201 measurements was within ±13%. Conclusion: This new method is simple and sensitive and has been applied successfully in a pharmacokinetic study of THJ-2201 in mouse plasma. The mean values of Tmax and Cmax were 0.25 h and 141.87 ± 12.11 ng/mL, respectively.

Background: A deep analytical study was performed on two different formats based on a “competitive” ELISA-type assay to develop a suitable, sensitive and cheap immune device for chloramphenicol determination that could be advantageously applied to the analysis of real matrices (pharmaceutical, food and environmental). Methods: To this purpose peroxidase enzyme as a marker and an amperometric electrode for hydrogen peroxide, as a transducer, were used. Through the first competitive format, chloramphenicol determination was based on the competition between chloramphenicol and conjugated with biotin-avidinperoxidase chloramphenicol, both free in solution, for anti-chloramphenicol immobilized in the membrane, while the second competitive format was based on the competition between free in solution chloramphenicol and immobilized in membrane one, for anti-chloramphenicol biotin-avidin-peroxidase conjugated free in solution. Results: The immunosensor was optimized by comparing the two used different “competitive” working formats on the basis of respective Kaff values, that were found to be about 105 and 104 (mol L-1)-1. The developed immune device displayed good selectivity for Chloramphenicol and LOD (limit of detection) was of the order of 10-9 mol L-1. The immunosensor was also used to test the presence of Chloramphenicol in real matrices such as cow milk, river wastewater and pharmaceutical formulations; recovery tests, using the standard addition method, gave satisfactory results. Conclusion: The results proved the validity of this immune device based on the competition between chloramphenicol and conjugated chloramphenicol obtained using biotin-avidin-peroxidase format, by which it is possible to carry out the analysis of chloramphenicol in milk and in river waste-waters with a % RSD ≤ 5 and with recovery values between 96% and 103%.

Background: A new and selective electrochemical sensor was developed for the determination of levocetirizine dihydrochloride, which is an antihistaminic drug. Methods: The investigation was performed by using cyclic, differential pulse and square wave voltammetric methods on the β-cyclodextrin modified glassy carbon electrode. It is thereby planned to obtain information about levocetirizine determination and its mechanism. Results: The efficiency of experimental parameters including pH, scan rate, and accumulation potential and time on the anodic response of levocetirizine dihydrochloride was studied. By employing the developed method and under optimized conditions, the current showed linear dependence with a concentration in the range between 2 × 10-8 M and 6 × 10-6 M in pH 2.0 Britton Robinson (BR) buffer. Conclusion: The achieved limits of detection and quantification were found as 3.73 × 10-10 M and 1.24 × 10-9 M, respectively. In addition, the possibility of applying the developed sensor for real sample analysis was investigated, so β-cyclodextrin modified glassy carbon electrode was used to determine levocetirizine dihydrochloride in Xyzal® tablet dosage form. Finally, this sensor was successfully applied to the real sample as a selective, simple, reproducible, repeatable electrochemical sensor.

Background: Modern pharmacological studies show that rhizoma coptidis has protective effects on the liver, gallbladder, kidney, cerebral ischemia-reperfusion, local hypoxia injury, antiinflammatory, bone injury, nerve cells and myocardial cells. The effective components have been isolated from picroside I, II, III and IV. Introduction: A selective and sensitive ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed for the simultaneous quantitative determination of picroside I, II, III and IV in rat plasma to aid the pharmacokinetics studies. Methods: Sprague-Dawley (SD) rats were orally administered with 10 mg/kg, intravenously injected with 1 mg/kg for the mixture of picroside I, II, III and IV. The biological samples were collected at 0.083 3 h, 0.25 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h. A UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) was used for chromatographic separation with the mobile phase consisting of acetonitrile and 0.1% formic acid by gradient elution. The flow rate was 0.4 mL/min. Multiple reaction monitoring (MRM) transitions were m/z 491.1→147.1 for picroside I, m/z 511.1→234.9 for picroside II, m/z 537.3→174.8 for picroside III and m/z 507.3→163.1 for picroside IV in negative ion mode. Results: The inter-day precision was less than 13%, the intra-day precision was less than 15%. The accuracy ranged from 89.4% to 111.1%. Recovery was higher than 79.1%, and the matrix effect ranged from 96.2% to 109.0%. Conclusion: The sensitive, rapid and selective UPLC-MS/MS method can be applied to the pharmacokinetic study of picroside I, II, III and IV in rats.