Journal of Pharmaceutical Analysis

2019, 9(2)

Abstract(98) PDF(4)

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An international journal providing a forum for original and pertinent contributions in Pharmaceutical Analysis.

Methodology of drug screening and target identification for new necroptosis inhibitors

Pengchao Pan, Zhenyu Cai, Chunlin Zhuang, Xiaofei Chen, Yifeng Chai

2019, 9(2): 71-76.

Abstract(122) PDF(2)

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Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.

Advancing USP compendial methods for fixed dose combinations: A case study of metoprolol tartrate and hydrochlorothiazide tablets

Qun Xu

2019, 9(2): 77-82.

Abstract(129) PDF(1)

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The current United States Pharmacopeia–National Formulary (USP–NF) includes more than 250 mono-graphs of fixed dose combinations (FDCs), and some of them need to be updated due to incompleteness of impurity profiles and obsolescence of analytical methodologies. A case study of metoprolol tartrate and hydrochlorothiazide tablets is presented to summarize challenges encountered during the USP monograph modernization initiative of FDCs and to highlight an "adoption and adaptation" approach employed for method development. To this end, a single stability-indicating HPLC method was devel-oped to separate the two drug substances and eight related compounds with resolution 2.0 or higher between all critical pairs. Chromatographic separations were achieved on a Symmetry column (C18, 100 mm × 4.6 mm, 3.5 μm) using sodium phosphate buffer (pH 3.0; 34 mM) and acetonitrile as mobile phase in a gradient elution mode. The stability-indicating capability of this method has been demon-strated by analyzing stressed samples of the two drug substances. The developed HPLC method was validated for simultaneous determination of metoprolol tartrate and hydrochlorothiazide and relevant impurities in the tablets. Moreover, the developed method was successfully applied to the analysis of commercial tablet dosage forms and proved to be suitable for routine quality control use. The case study could be used to streamline USP's monograph modernization process of FDCs and strengthen compendial procedures.

Production and stability study of a hospital parenteral nutrition solution for neonates

Anne-Laure Yailian, Céline Serre, Justine Fayard, Marina Faucon, Patrick Thomaré, Samira Filali, Christine Pivot, Florence Vételé, Fabrice Pirot, Emmanuelle Olivier

2019, 9(2): 83-90.

Abstract(106) PDF(1)

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Standard parenteral nutrition solutions are mixtures comprising interacting components that may de-grade themselves over time. The objective of this study was to investigate the physicochemical and microbiological stability of a hospital preparation for parenteral nutrition in neonatology. The analyses were performed throughout the storage of the preparations at 2–8 °C (up to 4 months). The extent of stability was based on the determination of amino acids dosage, visual and physicochemical properties (glucose and electrolytes concentrations, pH and osmolality measurements, particle counting) and mi-crobiological analysis (sterility test). A thermal degradation of ascorbic acid was conducted to evaluate the antioxidant properties of the parenteral mixture. Physicochemical and microbiological controls were found to comply with the specifications. Amino acids showed a good stability throughout the 4months storage except for cysteine, which was progressively degraded to cystine, conferring a yellow coloration to parenteral solutions. Parenteral nutrition standards solutions remain stable for 4 months at 2–8 °C, ensuring safe administration in preterm infants.

Identification of α-glucosidase inhibitors from Clinacanthus nutans leaf extract using liquid chromatography-mass spectrometry-based metabolomics and protein-ligand interaction with molecular docking

Suganya Murugesu, Zalikha Ibrahim, Qamar Uddin Ahmed, Bisha Fathamah Uzir, Nik Idris Nik Yusoff, Vikneswari Perumal, Faridah Abas, Khozirah Shaari, Alfi Khatib

2019, 9(2): 91-99.

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The present study used in vitro and in silico techniques, as well as the metabolomics approach to char-acterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. n-Hexane, n-hexane: ethyl acetate (1:1, v/v), ethyl acetate, ethyl acetate: methanol (1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square (PLS) statistical model was developed using the SIMCA P +14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one; (2) N-Isobutyl-2-nonen-6,8-diynamide; (3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and (4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase (PDB code: 3A4A) involved a hydrogen bond and some hydrophobic interactions be-tween the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335, and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313, VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.

Development of a fast and precise method for simultaneous quantification of the PLGA monomers lactic and glycolic acid by HPLC

Marcel Pourasghar, Aljoscha Koenneke, Peter Meiers, Marc Schneider

2019, 9(2): 100-107.

Abstract(82) PDF(1)

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Poly(lactide-co-glycolide acid) (PLGA) is an extraordinary well-described polymer and has excellent pharmaceutical properties like high biocompatibility and good biodegradability. Hence, it is one of the most used materials for drug delivery and biomedical systems, also being present in several US Food and Drug Administration-approved carrier systems and therapeutic devices. For both applications, the quantification of the polymer is inalienable. During the development of a production process, parameters like yield or loading efficacy are essential to be determined. Although PLGA is a well-defined biomaterial, it still lacks a sensitive and convenient quantification approach for PLGA-based systems. Thus, we present a novel method for the fast and precise quantification of PLGA by RP-HPLC. The polymer is hydrolyzed into its monomers, glycolic acid and lactic acid. Afterwards, the monomers are derivatized with the absorption-enhancing molecule 2,4′-dibromoacetophenone. Furthermore, the wavelength of the deri-vatized monomers is shifted to higher wavelengths, where the used solvents show a lower absorption, increasing the sensitivity and detectability. The developed method has a detection limit of 0.1 μg/mL, enabling the quantification of low amounts of PLGA. By quantifying both monomers separately, in-formation about the PLGA monomer ratio can be also directly obtained, being relevant for degradation behavior. Compared to existing approaches, like gravimetric or nuclear magnetic resonance measure-ments, which are tedious or expensive, the developed method is fast, ideal for routine screening, and it is selective since no stabilizer or excipient is interfering. Due to the high sensitivity and rapidity of the method, it is suitable for both laboratory and industrial uses.

Controlled delivery of ibuprofen from poly(vinyl alcohol)-poly (ethylene glycol) interpenetrating polymeric network hydrogels

Subhraseema Das, Usharani Subuddhi

2019, 9(2): 108-116.

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Hydrogels composed of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) were synthesized using glutaraldehyde as crosslinker and investigated for controlled delivery of the common anti-inflammatory drug, ibuprofen (IBF). To regulate the drug delivery, solid inclusion complexes (ICs) of IBF in β–cyclodextrin (β–CD) were prepared and added to the hydrogels. The ICs were prepared by the microwave irradiation method, which is more environmentally benign. The formation of IC was confirmed by various analytical techniques and the synthesized hydrogels were also characterized. Controlled release of drug was achieved from the hydrogels containing the ICs in comparison to the rapid release from hydrogels containing free IBF. The preliminary kinetic analysis emphasized the crucial role of β–CD in the drug release process that in-fluences the polymer relaxation, thereby leading to prolonged release. The cytotoxicity assay validated the hydrogels as non-toxic in nature and hence can be utilized for controlled delivery of IBF.

Application of activated carbon-decorated polyacrylonitrile nanofibers as an adsorbent in dispersive solid-phase extraction of fluoroquinolones from wastewater

K. Mogolodi Dimpe, Philiswa N. Nomngongo

2019, 9(2): 117-126.

Abstract(89) PDF(1)

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A cheap and simple sample preparation method, consisting of a dispersive solid-phase method and an ad-sorbent, activated carbon decorated PAN nanofibers, was employed and used for the extraction of antibiotics (ciprofloxacin, danofloxacin, and enrofloxacin) in wastewater. Electrospun PAN nanofibers that were deco-rated with activated carbon produced from waste tires were used as the solid phase and the antibiotics analyzed by using high-performance liquid chromatography. Parameters such as pH, mass of adsorbent (MA), extraction volume (EV), and extraction time (ET) were optimized owing to their potential effect on the extraction of antibiotics from water. The recovery of all antibiotics was satisfactory, in the range of 90%–99%. The limits of detection and quantification were 0.05, 0.11, 0.20, and 0.53, 1.21, 2.17 μg/L, respectively. The precision was determined from the repeatability and reproducibility and expressed as the intra-day (n = 20) and inter-day (n = 5) precision. The intra-day and inter-day precision was reported in terms of the per-centage relative standard deviation, which was 3% and 4%, respectively. The adsorption capacity of the ac-tivated carbon-decorated PAN nanofibers was satisfactory, and the reusability of the adsorbent was im-pressive when reused ten times. The accuracy of the dispersive solid phase extraction (DSPE) was validated by spike recovery tests; the results proved the reliability and efficiency of adsorbing antibiotics from was-tewater. Finally, the proposed method was applied to wastewater samples collected from a wastewater treatment plant, which included influent, secondary, and effluent wastewater.

Development of nitrogen and sulfur-doped carbon dots for cellular imaging

Hui Liu, Yue Zhang, Chengzhi Huang

2019, 9(2): 127-132.

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Heteroatom-doped carbon dots (CDs) have attracted extensive interest because of their improved elec-tronic and fluorescence properties with heteroatom doping. In this study, a new synthetic method for nitrogen (N) and sulfur (S) -doped CDs was developed via a hydrothermal method using methionine and citric acid as raw materials. The as-prepared CDs exhibit excellent optical properties and good bio-compatibility. The spherical N,S-doped CDs have an average diameter of 5 nm. They consist of C, O, N and S, and take on excellent water solubility due to the hydroxyl and carboxyl, amino groups on the surface. The CDs have a photoluminescence quantum yield of 13.8% using quinine sulfate as a reference; the average fluorescence lifetime of the CDs was 3.67 ns. The CDs solution present good photoluminescence properties, and the maximum excitation wavelength and emission wavelength locate at 330 nm and 405 nm, respectively. In addition, their fluorescence intensity almost does not change under the condi-tions of acid, alkali, and high salt, which indicated their anti-photobleaching property and good light stability. Based on the good biocompatibility and strong fluorescence emission of the CDs, they can be used as fluorescent imaging reagents.

Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

Rashmin khanam, Iram I. Hejazi, Syed Shahabuddin, Abdul R. Bhat, Fareeda Athar

2019, 9(2): 133-141.

Abstract(123) PDF(2)

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1, 3, 4-Oxadiazole derivatives (4a–5f) were previously synthesized to investigate their anticancer properties. However, studies relating to their antioxidant potential and signal transducer and activator of transcription (STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole de-rivatives (4a–5f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical (DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among al the derivatives, compound 5e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy re-leased in direct binding with the SH2 domain of STAT3 was the highest for compound 5e (-9.91kcal/mol). Through virtual screening, compound 5e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5e decreased the activation of STAT3 as observed with Western blot. In brief, compound 5e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

2019 Vol. 9, No. 2