Implementation of field detection devices for antimalarial quality screening in Lao PDR-A cost-effectiveness analysis.

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens.

The First Application of 1H NMR Spectroscopy for the Assessment of the Authenticity of Perfumes.

The manufacture of counterfeit goods is one of the world's largest underground businesses and is rapidly growing. Counterfeits can lead not only to the loss of profit for honest producers but also have a negative impact on consumers who pay excessive prices for poor quality goods that may result in health or safety problems. The perfume industry is constantly vulnerable to counterfeits, particularly in the fast developing market of "smell-alike" designer-inspired perfumes because these prompt the identification of the methods that classify their quality. In this paper, the application of proton nuclear magnetic resonance (1H NMR) spectroscopy is employed for the first time to authenticate perfumery products. The molecular composition of several types of authentic brand fragrances for women was compared with cheap inspired equivalents and fakes. Our approach offers the prospect of a fast and simple method for detecting counterfeit perfumes using 1H NMR spectroscopy.

The application of laboratory-based analytical tools and techniques for the quality assessment and improvement of commercial antivenoms used in the treatment of snakebite envenomation.

Snakebite envenomation is a public health problem of high impact, particularly for the developing world. Antivenom, which contains whole or protease-digested immunoglobulin G, purified from the plasma of hyper-immunized animals (mainly horses), is the mainstay for the treatment of snakebite envenomation. The success of antivenom therapy depends upon its ability to abrogate or reduce the local and systemic toxicity of envenomation. In addition, antivenom administration must be safe for the patients. Therefore, antivenom manufacturers must ensure that these products are effective and safe in the treatment of envenomations. Antivenom efficacy and safety are determined by the physicochemical characteristics of formulations, purity of the immunoglobulin fragments and antibodies, presence of protein aggregates, endotoxin burden, preservative load, and batch to batch variation, as well as on the ability to neutralize the most important toxins of the venoms against which the antivenom is designed. In this context, recent studies have shown that laboratory-based simple analytical techniques, for example, size exclusion chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, mass spectrometry, immunological profiling including immuno-turbidimetry and enzyme-linked immunosorbent assays, Western blotting, immune-chromatographic technique coupled to mass spectrometry analysis, reverse-phase high performance liquid chromatography, spectrofluorometric analysis, in vitro neutralization of venom enzymatic activities, and other methodologies, can be applied for the assessment of antivenom quality, safety, stability, and efficacy. This article reviews the usefulness of different analytical techniques for the quality assessment of commercial antivenoms. It is suggested that these tests should be applied for screening the quality of commercial antivenoms before their preclinical and clinical assessment.

Development of triaminotriazine functionalized graphene oxide capped chitosan porous composite beads for nutrients remediation towards water purification.

The porous, definite and nitrogen rich triaminotriazine (TAT) grafted graphene oxide (GO) known as TATGO composite was developed for nutrients (NO3- and PO43-) retention. Additionally, the structural property of TATGO composite was improved with the use of chitosan (CS) to produce easily separable TATGO@CS hybrid beads which possess the significant NO3- and PO43- adsorption capacities of 58.46 and 61.38 mg/g respectively than their individual materials. The instrumentations such as SEM, TGA, FTIR, EDAX, XRD and BET studies were executed for adsorbents. The optimization of the parameters accountable for adsorption process was performed in batch scale. The effect of isotherms (Langmuir, Freundlich and Dubinin-Radushkevich (D-R)), kinetics (pseudo-first/second order and particle/intraparticle diffusion) and thermodynamic parameters (ΔG°, ΔH° and ΔS°) of the adsorption was explored. The removal mechanism of TATGO@CS hybrid beads was to be electrostatic attraction on NO3- and PO43-. The field applicability and reuse of TATGO@CS hybrid beads was also inspected.

Hydrotropic Solubilization in Pharmaceutical Analysis: Origin, Evolution, Cumulative Trend and Precise Applications.

The hydrotropy though existing as precisely used scientific approach assisting solubilization for all. It took 66 long years to use the concept in drug analysis since its inception in 1916 and first use for facilitation of drug solubility toward better pharmaceutical analysis in 1982. Considering the unending importance in pharmaceutical sciences and thereby in analysis, it's a necessity to comprehensively outlook the origin, evolution, cumulative trend and precise applications in pharmaceutical analysis. Achieved hereby with chronological and comparative assessment of the studies published pertaining to solubility enhancement of poorly soluble drugs with use of hydrotropic agents alone or in combination for assisting pharmaceutical analysis. The thorough literature searches resulted into 77 references over a span of about 38 years. This comprehensive review critically evaluates existing literature; to our surprise we found Ibuprofen sodium, Lignocaine, Niacinamide and Metformin HCl as atypical hydrotropic agents. We also compared herein mono and mixed approaches which indicated prevalence of mono - hydrotropy over mixed. The possible mechanisms behind solubilization are presented for an additional insight. An essential effort has been made to state arbitrary classification to assist in future applications. The obvious purpose of this study was to collectively evaluate the crucial role of hydrotropic agents in pharmaceutical analyses for better drug delivery. This comprehensive review covers all details since inception to the updates till date which will definitely act as appropriate guideline for pharmaceutical analyst's in need of hydrotropy to assist pharmaceutical analysis for therapies today and tomorrow.

A handmade DNA extraction kit using laundry powder; insights on simplicity, cost-efficiency, rapidity, safety and the quality of purified DNA.

Here we describe an in-house kit for high throughput DNA extraction using laundry detergent. A simplified lysis buffer made only from 0.08 M EDTA, 0.1 M Tris, and laundry powder is the core of our protocol. We extracted genomic DNA from 150 µL of whole blood collected from different farm animals and compared the performance to both the DNeasy Blood & Tissue Kit (Qiagen) and the widely used salting-out procedure. An evaluation of the concentration and quality of the extracted DNA was then assessed by the NanoDrop absorption spectra, agarose gel migration, amplification in PCR and the Sanger sequencing. The in-house kit successfully extracted clean DNA from all blood samples, and discernably outperformed the commercial kits and the original salting-out procedure in the sense of the simplicity, cost-efficiency, quantity, and the quality of purified DNA. Apart from replacing proteinase K and the sodium dodecyl sulfate treatment by the laundry detergent, our protocol instructs a lysis buffer that eliminates sucrose, Triton X-100, MgCl2, NH4Cl, and KCl. Our handmade kit might be of interest for laboratories in underdeveloped countries with a budget shortage or applications in difficult field conditions, for example, when fridge storage for proteinase K cannot be ensured.

Rapid Screening α-Glucosidase Inhibitors from Natural Products by At-Line Nanofractionation with Parallel Mass Spectrometry and Bioactivity Assessment.

In this study, a novel at-line nanofractionation screening platform was successfully developed for the rapid screening and identification of α-glucosidase inhibitors from natural products. A time-course bioassay based on high density well-plates was performed in parallel with high resolution mass spectrometry (MS), providing a straightforward and rapid procedure to simultaneously obtain chemical and biological information of active compounds. Through multiple nanofractionations into the same well-plate and comparisons of the orthogonal separation results of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC), the α-glucosidase inhibitors can be accurately identified from co-eluates. The screening platform was comprehensively evaluated and validated, and was applied to the screenings of green tea polyphenols and Ginkgo folium flavonoids. After accurate peak shape and retention time matching between the bioactivity chromatograms and MS chromatograms, ten α-glucosidase inhibitors were successfully screened out and identified. The proposed screening method is rapid, effective and can avoid ignoring low abundant/active inhibitors.

Microfluidic Paper-Based Analytical Device for Histidine Determination.

A laminated paper-based analytical device (LPAD) for histidine detection was fabricated from a chromatography filtration paper and laminate films. Histidine recognition was effected by histidyl-tRNA synthetase (HisRS), and its detection was signaled colorimetrically based on the molybdenum blue reaction. The analytical conditions and detectable concentration range of histidine were examined. The method provided selective quantification from 1 to 100 µM histidine. LPAD fabrication is considerably simple, involving only the craft-cutting of the chromatography filtration paper and laminate film, and is cost-effective.

Finding a reliable limit of detection in the NIR determination of residual moisture in a freeze-dried drug product.

The validation of an analytical method in the pharmaceutical industry follows strictly regulated guidelines. The introduction of multivariable calibration methods requires a revision of these recommendations, since some of them are contradictory regarding the limit of detection (LOD). This work compares the LOD values obtained using pseudounivariate and multivariate procedures in the PLS-NIR determination of residual moisture content (RMC) in a freeze-dried drug. As NIR has proved to be more precise than Karl-Fischer at low RMC values, LOD has been estimated by ordinary and by orthogonal least squares regression. The precision of the RMC determination in approx. 2000 industrial vials was used as an indirect evidence of the reliability of the LOD values obtained. The effect of reducing the number of calibration samples and increasing the RMC values have also been studied. No significant differences were observed using a number of calibration samples ≥ 20. Based on our findings, when the size of the calibration sample set is high and the range of RMC values is close to the limit, the LOD estimated with the ICH formula and using orthogonal regression should be recommended. If water content moves away, the ICH formula should be replaced by the LODOS equation as a practical, reliable and simple procedure.

Reference-mean-centered statistical quality control.

Background: Statistical quality control (SQC) procedures generally use rejection limits centered on the stable mean of the results obtained for a control material by the analyzing instrument. However, for instruments with significant bias, re-centering the limits on a different value could improve the control procedures from the viewpoint of patient safety. Methods: A statistical model was used to assess the effect of shifting the rejection limits of the control procedure relative to the instrument mean on the number of erroneous results reported as a result of an increase in the systematic error of the measurement procedure due to an out-of-control condition. The behaviors of control procedures of type 1ks (k = 2, 2.5, 3) were studied when applied to analytical processes with different capabilities (σ = 3, 4, 6). Results: For measuring instruments with bias, shifting the rejection limits in the direction opposite to the bias improves the ability of the quality control procedure to limit the risk posed to patients in a systematic out-of-control condition. The maximum benefit is obtained when the displacement is equal to the bias of the instrument, that is, when the rejection limits are centered on the reference mean of the control material. The strategy is sensitive to error in estimating the bias. Shifting the limits more than the instrument's bias disproportionately increases the risk to patients. This effect should be considered in SQC planning for systems running the same test on multiple instruments. Conclusions: Centering the control rule on the reference mean is a potentially useful strategy for SQC planning based on risk management for measuring instruments with significant and stable uncorrected bias. Low uncertainty in estimating bias is necessary for this approach not to be counterproductive.

[Research progress in sample pretreatment and analytical techniques for cosmetics].

With the continuous economic development and improvement of living standards, cosmetic products are being widely used as daily consumer products, and there are increasing concerns about their safety. Consequently, there is a substantial increase in the number of cosmetic samples subjected to various analyses, and this in turn necessitates more stringent requirements for the related analytical techniques. However, traditional sample pretreatment and analytical techniques are time-consuming, require large amounts of organic solvents, and have low throughput, thus failing to meet the current demand for green analytical chemistry. To address this issue, researchers have developed numerous environmentally friendly pretreatment techniques as well as high-throughput and rapid on-site methods to ensure the quality and safety of cosmetics. This paper reviews the current progress in sample pretreatment and analytical techniques for cosmetics and discusses the trends and prospects, which may provide technical guidance for researchers and inspectors in the analysis of cosmetic products.

Chemical Identification and Confirmation of Contact Allergens.

Identification of the etiological chemical agent(s) associated with a case(s) of allergic contact dermatitis (ACD) is important for both patient management and public health surveillance. Traditional patch testing can identify chemical allergens to which the patient is allergic. Confirmation of allergen presence in the causative ACD-associated material is presently dependent on labeling information, which may not list the allergenic chemical on the product label or safety data sheet. Dermatologists have expressed concern over the lack of laboratory support for chemical allergen identification and possibly quantification from patients' ACD-associated products. The aim of this review was to provide the clinician a primer to better understand the analytical chemistry of contact allergen confirmation and unknown identification, including types of analyses, required instrumentation, identification levels of confidence decision tree, limitations, and costs.

Assessment of fish communities using environmental DNA: Effect of spatial sampling design in lentic systems of different sizes.

Freshwater fish biodiversity is quickly decreasing and requires effective monitoring and conservation. Environmental DNA (eDNA)-based methods have been shown to be highly sensitive and cost-efficient for aquatic biodiversity surveys, but few studies have systematically investigated how spatial sampling design affects eDNA-detected fish communities across lentic systems of different sizes. We compared the spatial patterns of fish diversity determined using eDNA in three lakes of small (SL; 3 ha), medium (ML; 122 ha) and large (LL; 4,343 ha) size using a spatially explicit grid sampling method. A total of 100 water samples (including nine, 17 and 18 shoreline samples and six, 14 and 36 interior samples from SL, ML and LL, respectively) were collected, and fish communities were analysed using eDNA metabarcoding of the mitochondrial 12S region. Together, 30, 35 and 41 fish taxa were detected in samples from SL, ML, and LL, respectively. We observed that eDNA from shoreline samples effectively captured the majority of the fish diversity of entire waterbodies, and pooled samples recovered fewer species than individually processed samples. Significant spatial autocorrelations between fish communities within 250 m and 2 km of each other were detected in ML and LL, respectively. Additionally, the relative sequence abundances of many fish species exhibited spatial distribution patterns that correlated with their typical habitat occupation. Overall, our results support the validity of a shoreline sampling strategy for eDNA-based fish community surveys in lentic systems but also suggest that a spatially comprehensive sampling design can reveal finer distribution patterns of individual species.

Basal serum luteinising hormone cut-off, and its utility and cost-effectiveness for aiding the diagnosis of the onset of puberty in girls with early stages of breast development.

OBJECTIVE: To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III). DESIGN, PATIENTS AND MEASUREMENTS: A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost-effectiveness analysis was performed. RESULTS: In comparison with basal LH cut-off of 0.3 IU/L, basal LH cut-off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut-off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut-off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost-saving when compared with using the cut-off of 0.3 IU/L. Moreover, using basal LH cut-off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients. CONCLUSIONS: Basal serum LH cut-off of 0.2 IU/L could be a simple and cost-saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.

Perspectives on the draft ICH M10 guidance: an interview with Kelly Dong.

Kelly Dong, PhD, Chief Executive Officer, United-Power Pharma Tech Co., Ltd Kelly Dong obtained her PhD degree from McGill University, Canada. Kelly has nearly 25 years of multinational industry experience working for pharmaceutical companies and CROs in Canada, the UK and China. Her scientific expertise encompasses drug metabolism and pharmacokinetics (DMPK) in drug discovery and regulated bioanalysis for preclinical and clinical development. After 20-year overseas experience, she joined GlaxoSmithKline R&D China in August 2009. She was the Director of DMPK for CNS drug discovery and Head of Bioanalysis, Immunogenicity and Biomarkers, overseeing more than 40 preclinical and clinical studies across different therapeutic areas. She joined United-Power Pharma as the Chief Executive Officer in February 2018. She is also a research fellow at the National Engineering Research Center of Protein Drugs. She is one of the founders and a steering committee member of China Bioanalysis Forum. She is also an active contributor to the scientific community, with numerous scientific publications, invited presentations and organizing scientific conferences. This interview was conducted by Sankeetha Nadarajah, Managing Commissioning Editor of Bioanalysis.

Plasmon-coupled 3D porous hotspot architecture for super-sensitive quantitative SERS sensing of toxic substances on real sample surfaces.

This paper reports a facile, fast, and cost-effective method for the synthesis of three-dimensional (3D) porous AgNPs/Cu composites as SERS substrates for the super-sensitive and quantitative detection of food organic contaminations. Due to the 3D porous hotspot architecture and the strong plasmonic coupling between Ag and Cu, the porous AgNPs/Cu substrate achieves ultrasensitive detection of multiple analytes as low as 10-11 M (crystal violet, CV), 10-9 M (malachite green, MG), 10-11 M (acephate), and 10-9 M (thiram) even with a portable Raman device. Moreover, this 3D solid substrate has good signal uniformity (RSD < 11%) and superior stability (<14% signal loss), allowing for practical SERS detections. Importantly, by simply wiping the real sample surface using the substrate, it successfully detects CV and MG residues on crayfish, and the limit of detection (LOD) of CV and MG is determined to be 1.14 × 10-9 M and 0.94 × 10-7 M, respectively. Further, the substrate can also be applied to detect acephate on eggplant with a LOD of 1.41 × 10-9 M and thiram on an apple surface with a LOD of 1.04 × 10-7 M. Note that all these SERS detections on real samples have a broad dynamic concentration range and a good linear dependence. As a "proof of concept", multi-component detection on a real sample has also been demonstrated. This 3D solid substrate possesses excellent detection sensitivity, diversity, and accuracy, which allows rapid and reliable determination of toxic substances in foods.

12th GCC Closed Forum: critical reagents; oligonucleotides; CoA; method transfer; HRMS; flow cytometry; regulatory findings; stability and immunogenicity.

The 12th GCC Closed Forum was held in Philadelphia, PA, USA, on 9 April 2018. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: critical reagents; oligonucleotides; certificates of analysis; method transfer; high resolution mass spectrometry; flow cytometry; recent regulatory findings and case studies involving stability and nonclinical immunogenicity. Conclusions and consensus from discussions of these topics are included in this article.

Microwave Assisted Synthesis of N-Doped Carbon Dots: an Easy, Fast and Cheap Sensor for Determination of Aspartic Acid in Sport Supplements.

In this work, determination of aspartic acid by N-doped carbon dots (N-CDs) was studied at optimum condition. Characterization and morphology of surface of N-CDs were carried out by FT-IR and HRTEM. N-doped carbon dots size was 10 nm. Quenching was very fast after addition of aspartic acid that is an important property of this sensor. Optimum conditions for pH and excitation wavelength were 8 and 360 nm, respectively. Linear dynamic range and limit of detection for aspartic acid were 0.5-50 µM and 90 nM, respectively. This method was used for aspartic acid determination in human serum and sport supplement powder as real samples. Performance of this sensor was also compared with other fluorescent sensors.