Development and Validation of Stability Indicating RP-HPLC Method for the Determination of Process and Degradation-Related Impurities in Sugammadex Sodium Drug Substance

The aim of this study is to develop and validate a sensitive and specific stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the quantitative determination of Sugammadex sodium together with its process and possible degradation impurities. The pKa value is 2.82. The chromatographic conditions have been optimized by the Hypersil Gold 250 mm X 4.6 mm, 3 µ RP-18 columns with gradient elution using a mobile phase composed of 0.1% phosphoric acid, acetonitrile, and methanol. The eluents were monitored at 205 nm with a flow rate of 1.0 mL/min with an injection volume of 20 µL. The optimized method produced symmetrical and sharp peaks with good separation between the process and degradation impurities. The forced degradation study was carried out under acid, base, oxidation, and thermal conditions to demonstrate the stability-indicating capability of the method. The method was validated as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) and showed excellent specificity, precision, linearity, accuracy, and robustness. The developed HPLC method was precise with a value of 0.25%. The relative standard deviation of accuracy represented by the recovery studies ranged between 89.5% and 104.6%. Linearity analyses indicated a correlation coefficient value of greater than 0.996 for Sugammadex and its known impurities. The LOD and LOQ values for Sugammadex ranged from 0.017% to 0.050%, and for its related impurities, they ranged from 0.015% to 0.055%. The stability of the analytical solution was evaluated and was stable for 75 h when stored at 5 °C. No chromatographic interference was observed during the degradation studies and also in the blank chromatogram.

     

Effect of Irradiation Absorbed Dose and Organic Solvent on the Grafting Rate of PVDF-g-PHEMA through Gamma-ray Irradiation in a Homogenous Solution

High Energy Chemistry - Modification of Polyvinylidene fluoride (PVDF) by radiation grafting is a research hotspot in recent years. In this study, the monomer 2-Hydroxyethyl methacrylate (HEMA) was...     

A FLATTENED OCTAHEDRON – THE METAL ENVIRONMENT IN COMPLEXES WITH PYRROLYL-SUBSTITUTED NITROXIDE DIRADICALS

Journal of Structural Chemistry - The structures of Ni(II), Cu(II), and Zn(II) complexes with anions of 2,5-pyrrolyl-disubstituted nitronyl nitroxide (L1) and iminonitroxide (L2) diradicals (HL1 is...     

Mechanochemical Synthesis of Layered Double Hydroxides as a Promising Method for the Preparation of Adsorbents and Catalysts

Kinetics and Catalysis - The results of studies in the field of synthesis and characterization of layered double hydroxides (LDHs) obtained using solid-phase reactions are summarized. The effect of...     

Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC–MS/LC–MS characterization,molecular docking and molecular dynamics simulation

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive viral disease outbreak of international concerns. The present study is mainly intended to identify the bioactive phytocompounds from traditional antiviral herb Houttuynia cordata Thunb. as potential inhibitors for three main replication proteins of SARS-CoV-2, namely Main protease (Mpro), Papain-Like protease (PLpro) and ADP ribose phosphatase (ADRP) which control the replication process. A total of 177 phytocompounds were characterized from H. cordata using GC–MS/LC–MS and they were docked against three SARS-CoV-2 proteins (receptors), namely Mpro, PLpro and ADRP using Epic, LigPrep and Glide module of Schrödinger suite 2020-3. During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of???7.274 and???5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788. Molecular Dynamics Simulation (MDS) performed using Desmond module of Schrödinger suite 2020–3 has demonstrated better stability in the ligand–receptor complexes A104-6LU7 and A166-6W02 within 100 ns than the A104-7JRN complex. The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP. Present findings confer opportunities for 6-Hydroxyondansetron and Quercitrin to be developed as new therapeutic drug against COVID-19.

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A NEW POLYMORPH OF THE [ReCl3(MeCN)(PPh3)2] COMPLEX AND ITS OXIDATION PRODUCTS

Journal of Structural Chemistry - A new polymorph of the [ReCl3(MeCN)(PPh3)2] complex is synthesized and characterized by single crystal X-ray diffraction (XRD). Its recrystallization from the...     

Reactivity of a N-Coordinated Germylene-Borane Complex: From Ge→B to Ge→Ga Coordination

Reactivity studies of the Ge^II→B complex L(Cl)Ge⋅BH₃ ( 1 ; L=2-Et₂NCH₂-4,6-tBu₂-C₆H₂) were performed to determine the effect on the Ge^II→B donation. N-coordinated compounds L(OtBu)Ge⋅BH₃ ( 2 ) and [LGe⋅BH₃]₂ ( 3 ) were prepared. The possible tuning of the Ge^II→B interaction was proved experimentally, yielding compounds 1-PPh₂-8-(LGe)-C₁₀H₆ ( 4 ) and L(Cl)Ge⋅GaCl₃ ( 5 ) without a Ge^II→B interaction. In 5 , an unprecedented Ge^II→Ga coordination was revealed. The experimental results were complemented by a theoretical study focusing on the bonding in 1 − 5 . The different strength of the Ge^II→E (E=B, Ga) donation was evaluated by using energy decomposition analysis. The basicity of different L(X)Ge groups through proton affinity is also assessed.     

Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

(O-Si)-Chelate acetic and benzoic acid N-(fluorosilylmethyl)amides: synthesis and structure

Russian Chemical Bulletin - New representatives of (O-Si)-chelate compounds, N-(fluorosilyl)methyl derivatives of N-methylacetamide, N-methylbenzamide, N-phenylacetamide, and N-phenylbenzamide,...     

Finite-Time Stabilization of Differential Systems with Incommensurable Delays

Differential Equations - For a spectrally controllable linear autonomous system with incommensurable delays, we construct a dynamic state feedback in the form of a differential-difference...