A novel domino protocol for three-component synthesis of new dibenzo[e,g]indoles: flexible intramolecular charge transfers

Fairly high yields of 2-aryl-3-nitrodibenzo[e,g]¬¬¬¬indoles were synthesized via a hitherto unreported domino-reaction of 9,10-phenanthrenequinone, ammonium acetate and β-nitrostyrenes in one pot. This novel three-component synthetic route is efficaciously catalysed by...

Crystal structure and Hirshfeld surface analysis of 3-(hydroxymethyl)-3-methyl-2,6-diphenylpiperidin-4-one

A new synthesis of the title compound, C19H21NO2, was developed with good yield and purity using the reaction of 4-hydroxy-3-methyl-2-butanone, benzaldehyde and ammonium acetate in glacial acetic acid as a solvent. The central piperidine ring adopts a chair conformation, and its least-squares basal plane forms dihedral angles of 85.71 (11) and 77.27 (11)° with the terminal aromatic rings. In the crystal, the molecules are linked by O—H...O and C—H...O hydrogen bonds into double ribbons. The Hirshfeld surface analysis shows that the most important contributions are from H...H (68%), C...H/H...C (19%) and O...H/H...O (12%) interactions.

A Greener Approach for Synthesis of Quinoline-3-carboxylate Building Block and their Biological Screening

The analogs of nitrogen-based heterocycles occupy an exclusive position as a value of more than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. Among many N-containing heterocycles, quinolines have become important due to their variety of applications in medicinal, synthetic organic chemistry as well as in the field of industrial chemistry. Present work gives information about the green and clean synthesis using multicomponent reactions (MCRs) methods and L-proline and ammonium acetate as a catalyst for the synthesis of quinoline derivatives. Synthesized quinoline derivatives undergo spectroscopic analysis and their biological evaluation.

Development and validation of a novel stability indicating HPLC method for the separation and determination of darolutamide and its impurities in pharmaceutical formulations

This study reports for the first time about a stability indicating RP-HPLC method for analysis of darolutamide and its impurities 1, 2, and 3 in bulk and formulations. The separation was achieved on Phenomenex column with Luna C18 (250 mm × 4.6 mm, 5 μm) as stationary phase, and 50 mM ammonium acetate: methanol solution 15:80 (v/v) at pH 5.2 as mobile phase at 1.0 mL/min flow rate. UV detection was carried at wavelength of 239 nm. In these conditions the retention time of darolutamide and its impurities 1, 2, and 3 was 7.05, 8.90, 4.63 and 5.95 min, respectively. The method was validated for system suitability, range of analysis, precision, specificity, stability, and robustness. Forced degradation study was done through exposure of the analyte to five different stress conditions and the % degradation was small in all degradation condition. The proposed method can separate and estimate the drug and its impurities in pharmaceutical formulations. Hence, the developed method was suitable for the quantification of darolutamide and can separate and analyse impurities 1, 2, and 3

The REVIEW ARTIKEL ANALISIS KANDUNGAN SILDENAFIL SITRAT DALAM SEDIAAN CAIR JAMU KUAT DENGAN METODE KROMATOGRAFI CAIR KINERJA TINGGI

Abstrak-Disfungsi ereksi merupakan masalah penting di seluruh dunia yang dialami hampir setengah dari pria diatas usia 40 tahun. Sebagian dari masyarakat Indonesia memilih untuk mengkonsumsi sediaan obat sildenafil sitrat yang dijual dipasaran untuk mengatasi disfungsi ereksi. Seiring dengan berkembangnya obat tradisional masyarakat cenderung lebih memilih mengonsumsi obat tradisional daripada obat sintetik. Obat tradisional atau yang lebih dikenal sebagai jamu yaitu bahan alam yang disediakan secara tradisional. Jamu dibuat dalam bentuk serbuk seduhan, pil, dan cairan. Jamu cair di Indonesia merupakan bentuk jamu paling disukai oleh masyarakat, dimana 59% konsumen nasional memilih jamu jenis ini. Perkembangan minat masyarakat yang besar terhadap produk jamu penambah stamina sering disalahgunakan produsen jamu yang dalam menambahkan bahan kimia obat (BKO). Pemakaian bahan kimia obat dalam jangka panjang menyebabkan toksisitas, salah satu BKO yang sering disalahgunakan adalah sildenafil sitrat, sildenafil sitrat untuk penggunaannya harus dengan pengawasan dokter serta dalam dosis yang tepat agar tidak menimbulkan toksisitas Review artikel ini bertujuan untuk mengidentifikasi dan menjawab permasalahan pada penerapan identifikasi sildenafil sitrat pada sediaan cair jamu kuat dengan menggunakan metode KCKT. Penerapan penelitian menggunakan metode naratif dari hasil pengelompokan data-data hasil review artikel yang sejenis sesuai dengan hasil yang digunakan untuk menjawab kebutuhan metode yang akan dipakai pada penelitian. Hasil review yang diperoleh sebanyak 8 artikel yang ditemukan yaitu metode KCKT dapat digunakan untuk mengidentifikasi kandungan bahan kimia obat sildenafil sitrat dalam sediaan cair jamu kuat dengan preparasi sampel menggunakan pelarut metanol, air, dan asetonitril dan mengandung buffer asam format 0,1 % kemudian dilakukan vortex dan ultrasonik dan sistem KCKT yang digunakan yaitu Fase gerak A (Acetonitrile):Fase gerak B (20 mmol/L ammonium acetate, 0.2% formic acid dan 10 mmol/L triethylamine) dengan elusi secara gradien Laju aliran di set 1,0 ml/menit, volume injesi 5 μL, suhu kolom diset 30˚C dan pada panjang gelombang 292 nm.

Development of High Performance Liquid Chromatographic Estimation of Domperidone and Lansoprazole

The combination of Domperidone and Lansoprazole is very useful in Gastro-esophageal disinfection (Dyspepsia). These methods provide means to separate the components characterize and quantify the components. An accurate, precise, specific and simple HPLC method was developed for simultaneous estimation of Domperidone and Lansoprazole. By this method retention time, linearity and accuracy data is respectively found for Domperidone and Lansoprazole. Mobile phase was prepared by mixing 51 volume of Acetonitrile and 49 volume of Ammonium Acetate (51:49 V/V) then 25mg each of Domperidone and Lansoprazole was dissolved in small volume of Acetonitrile: Ammonium Acetate (51:49 V/V) separately. Retention time was recorded 4.330 ± 0.003 minute and 5.820 ± 0.003 minute for Domperidone and Lansoprazole with 1.0 ml/min flow rate. The low value of % R.S.D indicates that this method is precise and accurate. Thus it can be concluded that the proposed method was good approach for obtaining reliable result.

Comparative pharmacokinetic study of bicalutamide administration alone and in combination with vitamin D in rats

Bicalutamide (BCL) has been approved for treatment of advanced prostate cancer (Pca), and vitamin D is inevitably used in combination with BCL in Pca patients for skeletal or anti-tumor strategies. Therefore, it is necessary to study the effect of vitamin D application on the pharmacokinetics of BCL. We developed and validated a specific, sensitive and rapid UHPLC–MS/MS method to investigate the pharmacokinetic behaviours of BCL in rat plasma with and without the combined use of vitamin D. Plasma samples were extracted by protein precipitation with ether/dichloromethane (2:1 v/v), and the analytes were separated by a Kinetex Biphenyl 100A column (2.1 × 100 mm, 2.6 μm) with a mobile phase composed of 0.5 mM ammonium acetate (PH 6.5) in water (A) and acetonitrile (B) in a ratio of A:B = 35:65 (v/v). Analysis of the ions was run in the multiple reactions monitoring (MRM) mode. The linear range of BCL was 5–2000 ng mL−1. The intra- and inter-day precision were less than 14%, and the accuracy was in the range of 94.4–107.1%. The mean extraction recoveries, matrix effects and stabilities were acceptable for this method. The validated method was successfully applied to evaluate the pharmacokinetic behaviours of BCL in rat plasma. The results demonstrated that the pharmacokinetic property of BCL is significantly affected by combined use of vitamin D, which might help provide useful evidence for the clinical therapy and further pharmacokinetic study.

Application of a HPLC-Q/TOF method with post-column compensation for separation and identification of polar impurities in Cytidine disodium triphosphate for injection

Background: Cytidine Disodium Triphosphate (CTP-2Na) for injection is mainly used for treating nervous system diseases. Currently, there are few studies focused on the separation and identification of polar impurities in CTP-2Na for injection, which is important for ensuring drug safety and efficacy. Objective: The study aimed to establish an HPLC-Q/TOF method for the separation and identification of polar impurities in CTP-2Na for injection. Methods: Chromatographic separation was achieved on a Waters Atlantis T3 column using 5 mM aqueous ammonium acetate solution as the mobile phase in an isocratic elution mode. A postcolumn compensation technology was used to improve the ionization efficiency of impurities in the spray chamber. Results: Three polar impurities (disodium cytidine tetraphosphate, disodium cytidine diphosphate, disodium cytidine monophosphate) were detected in CTP-2Na for injection. The former one is probably the overreaction product during the production of CTP-2Na, the latter two were reported as degradation products. The fragmentation patterns of cytidine phosphate compounds in negative ion mode are summarized. Conclusion: This study provides a good reference for the separation and identification of polar impurities in nucleotide drugs.

Influence of nickel on butanol production by Clostridium beijerinckii using hydrolyzate from green coconut shell

The improvement of biotechnological processes capable of transforming agro-industrial waste into products with high added value has stood out in the area of renewable energies, promoting positive impacts to the environment. Thus, the present work evaluated the influence of nickel on the conversion of fermentable sugars, present in the green coconut shell hydrolyzate (GCSH), into butanol and other products. Fermentation assays were performed at 37 °C, starting with 19.4 g.L-1 of sugars and 1.0 g.L-1 of inoculum (C. beijerinckii). The GCSH was supplemented with tryptone, yeast extract, ammonium acetate, minerals and phosphate buffer. Two conditions were tested: with and without addition of nickel. Concentrations of sugars (glucose and xylose), intermediate products (organic acids), acetone, butanol, and ethanol were determined by high performance liquid chromatography (HPLC). The results show that the butanol production was higher from GCSH without addition of nickel, reaching a concentration of 2.14 g.L-1 of butanol. Therefore, the presence of nickel in the hydrolyzate was not favorable in the production of butanol under the studied process conditions.