Measurement uncertainty in pharmaceutical analysis and its application

The measurement uncertainty provides complete information about an analytical result. This is very important because several decisions of compliance or non-compliance are based on analytical results in pharmaceutical industries. The aim of this work was to evaluate and discuss the estimation of uncertainty in pharmaceutical analysis. The uncertainty is a useful tool in the assessment of compliance or non-compliance of in-process and final pharmaceutical products as well as in the assessment of pharmaceutical equivalence and stability study of drug products.

The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis

Fluorescent nanoparticles have good chemical stability and photostability,controllable optical properties and larger stokes shift.In light of their designability and functionability,the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications.To enhance the sensitivity and selectivity,the combination of the fluorescent nanoparticles with the molecularly imprinted polymer,i.e.molecularly imprinted fluorescent nanoparticles(MIFN),was an effective way.The sensor based on MIFN(the MIFN sensor)could be more compatible with the complex sample matrix,which was especially widely adopted in medical and biological analysis.In this mini-review,the construction method,detective mechanism and types of MIFN sensors are elaborated.The current applications of MIFN sensors in pharmaceutical analysis,including pesticides/herbicide,veterinary drugs/drugs residues and human related proteins,are highlighted based on the literature in the recent three years.Finally,the research prospect and development trend of the MIFN sensor are forecasted.

Preface for Advances in Pharmaceutical Analysis 2017

The year of 2017 is of historic importance for China. It was the year that China started to step into New Period. It was also the year that I had joined Wuhan University as a Luojia professor and set up my research group for ten years since I came back to China from University of Notre Dame, United States in 2007.

Microneedle-based interstitial fluid extraction for drug analysis:Advances,challenges,and prospects

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Determination of Vitamin B_1 in Pharmaceutical Preparations by Flow-injection Analysis with Biamperometric Detection

A new electrochemical method for the on-line determination of vitamin B1 is presented. Based on dead-stop endpoint biamperometry by using two platinum foil electrodes with an applied potential difference of 150 mV, vitamin B1 can be oxidized by hexacyanoferrate （ Ⅲ ） in a sodium hydroxide medium via a reversible indicating couple Fe（ CN）6^4- /Fe（CN）6^3- The cell current is linear with the concentration of vitamin B1 in the concentration range of 4. 0 × 10^-6-1.0 × 10^ -3 mol/L with a detection limit of 8.0 ×10 ^-7 mol/L（0. 27 μg/mL）. Most familiar excipients, ions and vitamins do not interfere with the determination of vitamin B1. The method displays the advantages of simplicity, high efficiency（ 180 samples/h）, and high selectivity, and is suitable for the determination of vitamin B1 in pharmaceutical preparations.

Selective micellar electrokinetic chromatographic method for simultaneous determination of some pharmaceutical binary mixtures containing non-steroidal anti-inflammatory drugs

A simple and selective micellar electrokinetic chromatographic （MEKC） method has been developed for the analysis of five pharmaceutical binary mixtures containing three non-steroidal antiinflammatory drugs （NSAIDs）. The investigated mixtures were Ibuprofen （IP）-Paracetamol （PC）, Ibuprofen （IP）-Chlorzoxazone （CZ）, Ibuprofen （IP）Methocarbamol （MC）, Ketoprofen （KP） Chlorzoxazone （CZ） and Diclofenac sodium （DS）-Lidocaine hydrochloride （LC）. The separation was run for all mixtures using borate buffer （20 mM, pH 9） containing 15% （v/v） methanol and 100 mM sodium dodecyl sulphate （SDS） at 15 kV and the components were detected at 214 nm. Different factors affecting the electrophoretic mobility of the seven investigated drugs were studied and optimized. The method was validated according to international conference of harmonization （ICH） guidelines and United States pharmacopoeia （USP）. The method was applied to the analysis of five pharmaceutical binary mixtures in their dosage forms. The results were compared with other reported high performance liquid chromatographic methods and no significant differences were observed.

Determination of captopril in pharmaceutical preparation and biological fluids using two- and three-way chemometrics methods

Spectrophotometric method has been developed for the direct quantitative determination of captopril in pharmaceutical preparation and biological fluids （human plasma and urine） samples. The method was accomplished based on parallel factor analysis （PARAFAC） and partial least squares （PLS）. The study was carried out in the pH range from 2.0 to 12.8 and with a concentration from 0.70 to 61.50μg mL^-1 of captopril. Multivariate calibration models such as PLS at various pH and PARAFAC were elaborated from ultraviolet spectra deconvolution and captopril determination. The best models for this system were obtained with PARAFAC and PLS at pH 2.0. The applications of the method for determination of real samples were evaluated by analysis of captopril in pharmaceutical preparations and biological fluids with satisfactory results. The accuracy of the method, evaluated through the RMSEE was 0.5801 for captopril with best calibration curve by PARAFAC and 0.6168 for captopril with PLS at pH 2.0 model.

Determination of isoproterenol in pharmaceutical and biological samples using a pyrogallol red multiwalled carbon nanotube paste electrode as a sensor

Isoproterenol （ISPR） is an important catecholamine‐based drug that is widely used in the treatment of heart disease. However, overdose of this drug is very dangerous to the human body. In this study, a new sensor based on a pyrogallol red modified‐multiwalled carbon nanotube paste electrode （PGRMMWCNTPE） was prepared and used for high sensitivity determination of ISPR in aqueous solution. Electrocatalytic oxidation of ISPR at the PGRMMWCNTPE was investigated by chronoam‐perometry, cyclic voltammetry, and square‐wave voltammetry. The values of the catalytic rate con‐stant, electron transfer coefficient, and diffusion coefficient for ISPR oxidation were then calculated using voltammetric data. A linear calibration curve was constructed for ISPR concentration in the range 0.8–570μmol/L with a detection limit of 0.47μmol/L ISPR. The sensor was then applied to the determination of ISPR in urine and drug samples with satisfactory results.

Potentiometric determination of diclofenac in pharmaceutical formulation by membrane electrode based on ion associate with base dye

The characteristics, performance and application of membrane electrode based on ion associate of diclofenac with base dye Safranine T are described. The electrode response to diclofenac has the sensitivity of 47 ± 1.0 mV decade(?1) over the range of 5 × 10(?5) to 5 × 10(?2) mol/L at pH 6–12, and the detection limit of 3.2 × 10(?5) mol/L. The electrode is easy assembled at a relatively low cost has fast response time (2–4 s) and can be used for a period up to 3.5 months without any considerable divergence in potential. The proposed sensor displayed good selectivity for diclofenac in the presence of different substances. It was used to determine diclofenac in pharmaceuticals by means of the standard addition method.

Flow injection chemiluminescence determination of meloxicam using potassium permanganate and formaldehyde system

A simple, rapid and sensitive flow injection chemiluminescence （FI-CL） method has been developed for the determination of meloxicam. The method is based on the CL-emitting reaction between meloxicam and potassium permanganate in a hydrochloric acid medium, enhanced by formaldehyde （HCHO）. Under optimum conditions, calibration curve over the range of 1.0-20.0μg/mL was obtained. The proposed method was successfully applied to the determination of meloxicam in capsules with no evi- dence of interference from common excipients. The detection limit of this method was 25.6 ng/mL. The relative standard deviation was 2.1% for 10.0 μg/mL meloxicam. The sample throughput was found to be 120 samples/h.

Determination of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)purine in Rat Plasma,Urine and Liver Homogenates by High Performance Liquid Chromatography

Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)purine (Cyclo-D4G, IMGprodrug) in rat plasma, urine and liver homogenates. Methods Chromatography was performed with C-18Hypersil ODS column and a mobile phase of 7% (v/v) acetonitrile in phosphate buffer, pH 7.40, withUV detection at 283 nm. Results The average extraction recovery of Cyclo-D4G in rat plasma and urinewas 100.1% over its linear range of 0.5 - 80 μg·mL^(-1). The accuracy of the assay was 99.4% .The intra-and inter-day RSDs were less than 9.0% . Conclusion The analytical method was found to beapplicable, reliable and suitable for pharmacokinetic studies.

Spectrofluorimetric Method for the Determination of Triamcinolone Acetonide

A simple and highly sensitive method for the determination of triamcinolone acetonide in pharmaceutical formulations is presented. The approach is based on the fluorescence of production of triamcinolone acetonide oxidized by concentrated sulfuric acid. The effect of H2SO4, β-cyclodextrin (β-CD), solvent and cetyltrimethylammonium bromide (CTMAB) were discussed. And two analytical systems were established. One is CTMAB system, the linear range is 0–4.6×10?6 mol/L, and the detection limit is 3.59×10?8 mol/L. The other is β-CD and ethanol system, the linear range is 0–2.3×10?6 mol/L and the detection limit is 1.91×10?8 mol/L. The selectivity of analysis, the analytical figures of optimization, and the accuracy of the method are demonstrated with the determination of triamcinolone acetonide in pharmaceutical preparations. Key words triamcinolone acetonide - fluorimetry - CTMAB - β-cyclodextrin - pharmaceutical analysis CLC number O 657.39 Foundation item: Supported by the National Natural Science Foundation of China (20275028)Biography: Pan Zu-ting (1945-), male, Professor, research direction: analytical chemistry.

Anodic voltammetric determination of gemifloxacin using screen-printed carbon electrode

The electrochemical oxidation behavior and voltammetric assay of gemifloxacin were investigated using differential-pulse and cyclic voltammetry on a screen-printed carbon electrode.The effects of pH,scan rates,and concentration of the drug on the anodic peak current were studied.Voltammograms of gemifloxacin in Tris-HCl buffer（pH 7.0） exhibited a well-defined single oxidation peak.A differential-pulse voltammetric procedure for the quantitation of gemifloxacin has been developed and suitably validated with respect to linearity,limits of detection and quantification,accuracy,precision,specificity,and robustness.The calibration was linear from 0.5 to 10.0 μM,and the limits of detection and quantification were 0.15 and 5.0 μM.Recoveries ranging from 96.26% to 103.64% were obtained.The method was successfully applied to the determination of gemifloxacin in pharmaceutical tablets without any pre-treatment.Excipients present in the tablets did not interfere in the assay.

Electrogenerated chemiluminescence sensor for the determination of metoclopramide using ordered mesoporous carbon for immobilizing tris(2,2'-bipyridyl)ruthenium

A novel electrogenerated chemiluminescence(ECL)sensor for the determination of metoclopramide was developed by employing ruthenium complex as an ECL signal producer and an ordered mesoporous carbon(OMC)material as modified material.The ECL sensor was fabricated by adsorption ruthenium complex into a mixture of OMC and Nafion,which showed good electrochemical and ECL behaviors.It was found that the ECL intensity of the sensor fabricated was greatly enhanced in the presence of metoclopramide.Based on this finding,a highly sensitive and reproducible ECL method was developed for the determination of metoclopramide.The result showed that the ECL intensity was linear with the concentration of metoclopramide in the range from 1.0×10-10 to 5.0×10-7M and the detection limit was 3×10-11M.The ECL sensor exhibited a long-term stability and a fine reproducibility with relative standard deviation of 1.0 % for 1.0×10-10M metoclopramide in 18 continuous determinations.The developed method has been applied to the determination of metoclopramide in tablet samples with satisfactory results.

Synthesis of carbon nanosheet from barley and its use as non-enzymatic glucose biosensor

In this work,carbon nanosheet（CNS） based electrode was designed for electrochemical biosensing of glucose.CNS has been obtained by the pyrolysis of barley at 600-750℃ in a muffle furnace：it was then purified and functionalized.The CNS has been characterized by scanning electron microscopy（SEM）.X-ray diffraction（XRD） and Raman spectroscopic techniques.The electrochemical activity of CNS-based electrode was investigated by linear sweep vollammetry（LSV） and square wave voltammetry（SWV）,for the oxidation of glucose in 0.001 M H2SO4（pH 6.0）.The linear range of the sensor was found to be 10-4-10-6M（1-100 μM） within the response time of 4 s.Interestingly,its sensitivity reached as high as 26.002±0.01 μA/μM cm2.Electrochemical experiments revealed that the proposed electrode offered an excellent electrochemical activity towards the oxidation of glucose and could be applied for the construction of non-enzymatic glucose biosensors.

Spectrophotometric Study for the Reaction of Pentoxifylline Hydrochloride with 1,2-Naphthoquinone-4-Sulphonate: Kinetics, Mechanism and Application for Development of High-Throughput Kinetic Microwell Assay for Pentoxifylline in Quality Control Laboratory

Spectrophotometric study was carried out, for the first time, to investigate the reaction between the vasodilator pentoxifylline hydrochloride (POX) and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. The reaction occurs in alkaline medium to activate the nucleophilic substitution reaction producing an orange-colored product measured spectrophometrically at λmax 472 nm. The variables affecting the reaction were carefully studied and the conditions were optimized. The kinetics of the reaction was investigated and its activation energy was found to be 0.262 cal/mol. Owing to its low activation energy, the reaction proceeded easily and was successfully used for simple and rapid assay of POX. The stoichiometry of the reaction was determined (1:1), and the reaction mechanism was suggested. To develop a high-throughput methodology used in quality control laboratory, a comparative study of the reaction using the conventional spectrophotometric versus microwell assay was applied. Under the optimum reaction conditions, the initial rate and fixed time methods were utilized for constructing the calibration graphs for determination of POX concentrations. The linear range was 10 - 120 μg/ml with good correlation coefficients (0.9987 - 0.9998). The LOD was 2.5 and 3.4 μg/ml for initial rate and fixed time methods, respectively. The intra- and inter-day accuracy and precision of the developed methods were satisfactory, where RSD was ≤3.94%. The present methods have been successfully applied to the determination of POX in its pharmaceutical tablets, and the percentage recovery values were 97.9% - 101.9%. Therefore, we strongly recommend the proposed methods for determination of POX in quality control laboratories.

TWO-DIMENSIONAL LIQUID CHROMATOGRAPHY(2D-LC) IN THE ANALYSIS OF PHARMACEUTICALS AND AUTHENTICATION OF CHINESE HERBAL MEDICINE

One-dimensional liquid chromatography(1D-LC)is routinely applied to the analysis of all kinds of samples in different fields.With the introduction of UHPLC instruments and sub-2micron particle columns,the separation efficiency was greatly improved.To resolve all components of complex samples,however,1D-LC does not provide enough resolving power,or peak capacity.In addition,to separate compounds co-eluting in 1D-LC,increasing the separation efficiency by increasing

Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform

Antimicrobial resistance(AMR)has become a global health crisis in need of novel solutions.To this end,antibiotic combination therapies,which combine multiple antibiotics for treatment,have at-tracted significant attention as a potential approach for combating AMR.To facilitate advances in anti-biotic combination therapies,most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however,there remains a need for automated high-throughput plat-forms that can create and examine antibiotic combinations on-demand,at scale,and with minimal reagent consumption.To address these challenges,we have developed a Robotic-Printed Combinatorial Droplet(RoboDrop)platform by integrating a programmable droplet microfuidic device that generates antibiotic combinations in nanoliter droplets in automation,a robotic arm that arranges the droplets in an array,and a camera that images the array of thousands of droplets in parallel.We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing.As a demonstration,we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin,penicillin,and oxacillin against a model E.coli strain.We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.

Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis;however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis,including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids,omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathwayrelated reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

UFLC-DAD-ESI-IT-TOFMSn Analysis on Biotransformation of Tongmai Formula Incubated with Human Intestinal Bacteria

Objective To investigate the biotransformation of Tongmai formula（TMF） in incubated system of human intestinal flora（HIF）. Methods The technique of ultra fast liquid chromatography with diode array detector and coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry（UFLC-DAD-ESIIT-TOFMSn） was adopted to determine the products of TMF biotransformed by HIF. Results Totally 66 constituents were detected and identified according to the accurate mass measurements（〈 5 ppm） and effective MSn fragment ions. Meanwhile, the potential biotransformational pathways of compounds in TMF transformed by HIF were firstly proposed. Desugarization, hydroxylation, and methylation were the major reactions in the biotransformation mechanism of TMF by HIF. Conclusion This study will be helpful to clarify the material basis of pharmacological activities from TMF in vivo.