Paper Analytic Device to Detect the Presence of Four Chemotherapy Drugs

A paper analytic device, the chemoPAD, was developed and validated to visually detect methotrexate, doxorubicin, cisplatin, and oxaliplatin at concentrations commonly found in injectable dosage forms. By testing residual solution after patient treatment, the chemoPAD can be used to monitor drug quality without restriction of patient access to medication. The chemoPAD is produced by wax printing on Ahlstrom paper to create separate reaction areas and deposits small amounts of chemicals to create color changes in response to different active pharmaceutical ingredients (APIs). This creates a unique color bar code to identify each medication. Internal validation studies show that the chemoPAD has excellent sensitivity and specificity to differentiate between samples of 100% and 0% API, which is the distinction relevant to the majority of reported falsified chemotherapy cases. The platinum-containing drugs, cisplatin and oxaliplatin, can be detected semiquantitatively. The cards can be read either visually by comparison with a standard image or by using computer image analysis. Dosage forms were collected from the Ethiopian health care system and analyzed with the chemoPAD followed by high-performance liquid chromatography. A substandard sample was discovered and reported to the Ethiopian Food Medicine and Healthcare Administration and Control Authority.

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N-nitrosamine Impurities in Medicines: Toxicity, Formation Pathways, Methods of Determination, and Limits (Review)

Drug development & registration ◽

10.33380/2305-2066-2020-9-4-180-190 ◽

2020 ◽

Vol 9 (4) ◽

pp. 180-190

Author(s):

P. P. Shchetinin ◽

S. P. Senchenko ◽

K. K. Gordeev

Keyword(s):

High Performance ◽

Pharmaceutical Products ◽

Gas Chromatography Mass Spectrometry ◽

Medicinal Products ◽

Angiotensin Ii Receptor ◽

Pharmaceutical Ingredients ◽

Current State ◽

Golden Standard ◽

Receptor Blockers ◽

And Control

Introduction. N-nitrosamine compounds are potent genotoxic agents in animal species and some are classified as probable human carcinogens. This group of genotoxic impurities was found in drugs such as angiotensin II receptor blockers, histamine H1 receptor antagonists, and synthetic antidiabetic drugs. This discovery caused a flurry of alarm in the global pharmaceutical industry and resulted in a series of international investigations trying to determine root causes of nitrosamine formation in medicinal products and to find ways to minimize risks associated with nitrosamine contamination.Text. This paper provides an overview of the current state of the problem. It summarises the main pathways of N-nitrosamine formation in medicinal products at the stages from synthesis of active pharmaceutical ingredients to storage of finished pharmaceutical products. The paper describes the main mechanism responsible for the toxic effect of this group of impurities in human body. It also describes methods of extraction and analysis of N-nitrosamines found in medicinal products. It was demonstrated that high-performance liquid chromatography and gas chromatography-mass spectrometry are a golden standard for the detection of these contaminants. The paper also touches upon the main principles of setting limits for nitrosamine impurities in medicinal products.Conclusion. The data presented give a picture of the root causes of N-nitrosamine formation in medicinal products, as well as current detection and control methods used worldwide. Meanwhile, the paper raises a key issue about the need to develop Russian standards that would control the purity of medicinal products in terms of N-nitrosamine impurities. For that end, it will be necessary to draw on the experience of the leading USA and EU regulatory authorities.

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Substandard Cisplatin Found While Screening the Quality of Anticancer Drugs From Addis Ababa, Ethiopia

JCO Global Oncology ◽

10.1200/jgo.19.00365 ◽

2020 ◽

pp. 407-413 ◽

Cited By ~ 1

Author(s):

Madeline S. Eberle ◽

Ayenew Ashenef ◽

Heran Gerba ◽

Patrick J. Loehrer ◽

Marya Lieberman

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

High Performance ◽

Addis Ababa ◽

Dosage Forms ◽

False Positives ◽

Drug Quality ◽

Chemotherapy Drugs ◽

Analytical Device

PURPOSE A postmarket evaluation of chemotherapy dosage forms in Ethiopia was conducted to test the accuracy of the chemoPAD, a paper analytical device for drug quality screening. MATERIALS AND METHODS In September of 2018 in Addis Ababa, Ethiopia, 41 anticancer drug dosage forms (representing 4 active ingredients, 5 brands, and 7 lot numbers) were collected and were rapidly screened for quality using a chemotherapy paper analytical device (chemoPAD). Confirmatory analysis via high performance liquid chromatography was conducted. RESULTS The chemoPAD showed that the correct active pharmaceutical ingredient was present in doxorubicin, methotrexate, and oxaliplatin injectable dosage forms. However, 11 of 20 cisplatin samples failed the screening test. Confirmatory assay by high-performance liquid chromatography showed that all 20 cisplatin samples—comprising three lot numbers of a product stated to be Cisteen—were substandard, containing on average 54% ± 6% of the stated cisplatin content. Inductively coupled plasma optical emission spectroscopy analysis of five representative samples found 57% to 71% of the platinum that should have been present. The sensitivity of the chemoPAD for detection of falsified products could not be measured (as none were present in these samples), but the selectivity was 100% (no false positives). The sensitivity for detection of substandard products was 55%, and the selectivity was 100% (no false positives). CONCLUSION Although instrumental analysis by pharmacopeia methods must remain the gold standard for assessing overall drug quality, these methods are time consuming and patients could be exposed to a bad-quality drug while clinical workers wait for testing to be performed. The chemoPAD technology could allow clinicians to check at the point of use for serious problems in the quality of chemotherapy drugs on a weekly or monthly schedule.

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Reversed-Phase High Performance Liquid Chromatographic Analysis of Three First Line Anti-Tuberculosis Drugs

Revista de Chimie ◽

10.37358/rc.18.12.6799 ◽

2019 ◽

Vol 69 (12) ◽

pp. 3590-3592

Author(s):

Nela Bibire ◽

Romeo Iulian Olariu ◽

Luminita Agoroaei ◽

Madalina Vieriu ◽

Alina Diana Panainte ◽

...

Keyword(s):

High Performance ◽

Biological Fluids ◽

Gradient Elution ◽

High Performance Liquid Chromatographic ◽

Reversed Phase ◽

Assay Method ◽

Active Pharmaceutical Ingredients ◽

First Line ◽

Pharmaceutical Ingredients ◽

Liquid Chromatographic

Active pharmaceutical ingredients such as isoniazid, pyrazinamide and rifampicin are among the most important first-line anti-tuberculosis drugs. A simple, rapid and sensitive reversed phase-high performance liquid chromatographic assay method for the simultaneous determination of isoniazid, pyrazinamide and rifampicin has been developed. Separation of the interest compounds was achieved in a 10 min chromatographic run in gradient elution mode on a Zorbax SB-C18 stainless steel column (150 � 4 mm, 5 mm) using a guard column containing the same stationary phase. The gradient elution was carried out with a mobile phase of 10% CH3CN aqueous solution for channel A and 50% CH3CN in pH = 6.8 phosphate buffer (20 mM), to which 1.5 mL triethylamine were added for channel B. Quantification of the analyzed substances was carried out spectrophotometrically at 269 nm. Detection limits of 0.48 mg/L for isoniazid, 0.52 mg/L for pyrazinamide and 0.48 mg/L for rifampicin were established for the developed assay method. The present work showed that the proposed analysis method was advantageous for simple and rapid analysis of the active pharmaceutical ingredients in pharmaceuticals and biological fluids.

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ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

Current Analytical Chemistry ◽

10.2174/1573411016999200802024151 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1106-1112

Author(s):

Ibrahim A. Darwish ◽

Nasr Y. Khalil ◽

Mohammad AlZeer

Keyword(s):

High Performance ◽

Kinase Inhibitor ◽

Degradation Products ◽

Internal Standard ◽

Dosage Forms ◽

Uv Detector ◽

Stability Indicating ◽

Therapeutic Benefits ◽

Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

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Reduction of Polycyclic Aromatic Hydrocarbons (PAHs) in Sesame Oil Using Cellulosic Aerogel

Foods ◽

10.3390/foods10030644 ◽

2021 ◽

Vol 10 (3) ◽

pp. 644

Author(s):

Do-Yeong Kim ◽

Boram Kim ◽

Han-Seung Shin

Keyword(s):

Polycyclic Aromatic Hydrocarbons ◽

Aromatic Hydrocarbons ◽

High Performance ◽

Oil Quality ◽

Acid Value ◽

Quality Parameters ◽

Sesame Oil ◽

Miscanthus Sinensis ◽

Polycyclic Aromatic ◽

And Control

The effect of cellulosic aerogel treatments used for adsorption of four polycyclic aromatic hydrocarbons (PAHs)—benzo[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene [BaP])—generated during the manufacture of sesame oil was evaluated. In this study, eulalia (Miscanthus sinensis var. purpurascens)-based cellulosic aerogel (adsorbent) was prepared and used high performance liquid chromatography with fluorescence detection for determination of PAHs in sesame oil. In addition, changes in the sesame oil quality parameters (acid value, peroxide value, color, and fatty acid composition) following cellulosic aerogel treatment were also evaluated. The four PAHs and their total levels decreased in sesame oil samples roasted under different conditions (p < 0.05) following treatment with cellulosic aerogel. In particular, highly carcinogenic BaP was not detected after treatment with cellulosic aerogel. Moreover, there were no noticeable quality changes in the quality parameters between treated and control samples. It was concluded that eulalia-based cellulosic aerogel proved suitable for the reduction of PAHs from sesame oil and can be used as an eco-friendly adsorbent.

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Advanced high-performance processing tools for diagnostics and control in fusion devices

Fusion Engineering and Design ◽

10.1016/j.fusengdes.2021.112529 ◽

2021 ◽

Vol 170 ◽

pp. 112529

Author(s):

N. Cruz ◽

A.J.N. Batista ◽

J.M. Cardoso ◽

B.B. Carvalho ◽

P.F. Carvalho ◽

...

Keyword(s):

High Performance ◽

Diagnostics And Control ◽

And Control

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Detection of Antimicrobial Residues in Poultry Litter: Monitoring a Risk through a Selective and Sensitive HPLC–MS/MS Method

Animals ◽

10.3390/ani11051399 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1399

Author(s):

Karina Yévenes ◽

Ekaterina Pokrant ◽

Lina Trincado ◽

Lisette Lapierre ◽

Nicolás Galarce ◽

...

Keyword(s):

High Performance ◽

Limit Of Detection ◽

Poultry Litter ◽

Chromatography Tandem Mass Spectrometry ◽

Antimicrobial Residues ◽

Field Samples ◽

Liquid Chromatography Tandem Mass ◽

Commercial Poultry ◽

Agriculture Fertilizer ◽

And Control

Tetracyclines, sulphonamides, and quinolones are families of antimicrobials (AMs) widely used in the poultry industry and can excrete up to 90% of AMs administrated, which accumulate in poultry litter. Worryingly, poultry litter is widely used as an agriculture fertilizer, contributing to the spread AMs residues in the environment. The aim of this research was to develop a method that could simultaneously identify and quantify three AMs families in poultry litter by high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). Samples of AMs free poultry litter were used to validate the method according to 657/2002/EC and VICH GL49. Results indicate that limit of detection (LOD) ranged from 8.95 to 20.86 μg kg−1, while limits of quantitation (LOQ) values were between 26.85 and 62.58 µg kg−1 of tetracycline, 4-epi-tetracycline, oxytetracycline, 4-epi-oxytetracycline, enrofloxacin, ciprofloxacin, flumequine, sulfachloropyridazine, and sulfadiazine. Recoveries obtained ranged from 93 to 108%. The analysis of field samples obtained from seven commercial poultry flocks confirmed the adequacy of the method since it detected means concentrations ranging from 20 to 10,364 μg kg−1. This provides us an accurate and reliable tool to monitor AMs residues in poultry litter and control its use as agricultural fertilizer.

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A Novel Fast-Locking ADPLL Based on Bisection Method

Electronics ◽

10.3390/electronics10121382 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1382

Author(s):

Xiaoying Deng ◽

Huazhang Li ◽

Mingcheng Zhu

Keyword(s):

High Performance ◽

Tuning Range ◽

Frequency Control ◽

Control Word ◽

Cmos Process ◽

Bisection Method ◽

Reference Frequency ◽

Wide Tuning Range ◽

Cascade Structure ◽

And Control

Based on the idea of bisection method, a new structure of All-Digital Phased-Locked Loop (ADPLL) with fast-locking is proposed. The structure and locking method are different from the traditional ADPLLs. The Control Circuit consists of frequency compare module, mode-adjust module and control module, which is responsible for adjusting the frequency control word of digital-controlled-oscillator (DCO) by Bisection method according to the result of the frequency compare between reference clock and restructure clock. With a high frequency cascade structure, the DCO achieves wide tuning range and high resolution. The proposed ADPLL was designed in SMIC 180 nm CMOS process. The measured results show a lock range of 640-to-1920 MHz with a 40 MHz reference frequency. The ADPLL core occupies 0.04 mm2, and the power consumption is 29.48 mW, with a 1.8 V supply. The longest locking time is 23 reference cycles, 575 ns, at 1.92 GHz. When the ADPLL operates at 1.28 GHz–1.6 GHz, the locking time is the shortest, only 9 reference cycles, 225 ns. Compared with the recent high-performance ADPLLs, our design shows advantages of small area, short locking time, and wide tuning range.

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Effects of Camu-Camu (Myrciaria dubia) Powder on the Physicochemical and Kinetic Parameters of Deteriorating Microorganisms and Salmonella enterica Subsp. enterica Serovar Typhimurium in Refrigerated Vacuum-Packed Ground Beef

Agriculture ◽

10.3390/agriculture11030252 ◽

2021 ◽

Vol 11 (3) ◽

pp. 252

Author(s):

Jorge Luiz da Silva ◽

Vasco Cadavez ◽

José M. Lorenzo ◽

Eduardo Eustáquio de Souza Figueiredo ◽

Ursula Gonzales-Barron

Keyword(s):

Ground Beef ◽

Treated Group ◽

B Value ◽

Kinetics Parameters ◽

Psychrotrophic Bacteria ◽

Color Changes ◽

A Value ◽

Spoilage Bacteria ◽

Serovar Typhimurium ◽

And Control

This study aims to evaluate the effects of camu-camu powder (CCP), Amazonian berry fruit with documented bioactive properties, physicochemical meat parameters, and the growth kinetics parameters of S. enterica ser. Typhimurium, psychrotrophic bacteria (PSY), and lactic acid bacteria (LAB) in vacuum-packed ground beef. Batches of ground beef were mixed with 0.0%, 2.0%, 3.5%, and 5.0% CCP (w/w), vacuum-packed as 10 g portions, and stored at 5 °C for 16 days. Centesimal composition analyses (only on the initial day), pH, TBARS, and color were quantified on storage days 1, 7, and 15, while PSY and LAB were counted on days 0, 3, 6, 9, 13, and 16. Another experiment was conducted with the same camu-camu doses by inoculating S. enterica ser. Typhimurium microbial kinetic curves were modeled by the Huang growth and Weibull decay models. CCP decreased TBARS in beef from 0.477 to 0.189 mg MDA·kg−1. No significant differences in meat pH between treated and control samples were observed on day 15. CCP addition caused color changes, with color a* value decreases (from 14.45 to 13.44) and color b* value increases (from 17.41 to 21.25), while color L* was not affected. Higher CCP doses caused progressive LAB growth inhibition from 0.596 to 0.349 log CFU·day−1 at 2.0% and 5.0% CCP, respectively. Similarly, PSY growth rates in the treated group were lower (0.79–0.91 log CFU·day−1) compared to the control (1.21 log CFU·day−1). CCP addition at any of the investigated doses produced a steeper S. enterica ser. Typhimurium inactivation during the first cold storage day, represented by Weibull’s concavity α shape parameter, ranged from 0.37 to 0.51, in contrast to 1.24 for the control. At the end of the experiment, however, S. enterica ser. Typhimurium counts in beef containing CCP were not significantly different (p < 0.05) from the control. Although CCP affects bacterial kinetics, it does not protect ground beef against spoilage bacteria and Salmonella to the same degree it does against lipid peroxidation.

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