HPLC and chemometrics-assisted UV-spectroscopy methods for the simultaneous determination of ambroxol and doxycycline in capsule

High-performance liquid chromatography (HPLC) and multivariate spectrophotometric methods are described for the simultaneous determination of ambroxol hydrochloride (AM) and doxycycline (DX) in combined pharmaceutical capsules. The chromatographic separation was achieved on reversed-phase C(18) analytical column with a mobile phase consisting of a mixture of 20mM potassium dihydrogen phosphate, pH 6-acetonitrile in ratio of (1:1, v/v) and UV detection at 245 nm. Also, the resolution has been accomplished by using numerical spectrophotometric methods as classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-1) applied to the UV spectra of the mixture and graphical spectrophotometric method as first derivative of the ratio spectra ((1)DD) method. Analytical figures of merit (FOM), such as sensitivity, selectivity, analytical sensitivity, limit of quantitation and limit of detection were determined for CLS, PLS-1 and PCR methods. The proposed methods were validated and successfully applied for the analysis of pharmaceutical formulation and laboratory-prepared mixtures containing the two component combination.     

Stability-indicating thin-layer chromatographic method for quantitative determination of ribavirin

A simple and accurate stability-indicating thin-layer chromatographic (TLC) method is developed and validated for the quantitative determination of ribavirin (RBV) in its bulk and with used for development consists of chloroform-methanol-acetic acid (60:15:15, v/v/v). The separated spots are visualized as bluish green spots after being sprayed with anisaldehyde reagent. RBV is subjected to different accelerated stress conditions. The drug is found to undergo degradation under all stress conditions, and the degradation products are well resolved from the pure drug with significantly different Rf values. The optical densities of the separated spots are found to be linear with the amount of RBV in the range of 5-40 microg/spot with a good correlation coefficient (r=0.9980). The limit of detection and limit of quantitation values are 1.40 and 4.67 microg/spot, respectively. Statistical analysis proves that the method is repeatable and accurate for the determination of RBV in the presence of its degradation products. The method meets the International Conference on Harmonisation/Food and Drug Administration regulatory requirements. The proposed TLC method is successfully applied for the determination of RBV, pure and in capsules, with good accuracy and precision; the label claim percentages are 98.8%+/-1.5%. The results obtained by the proposed TLC method are comparable with those obtained by the official method.     

Triplet energy transfers in electrostatic host-guest assemblies of unsaturated organometallic cluster cations and carboxylate-containing porphyrin pigments

The unsaturated cyclic [M3(dppm)3(CO)](2+) clusters (M = Pt, Pd; dppm = Ph2PCH2PPh2; such as PF6(-) salt) exhibit a cavity formed by the six dppm-phenyl groups placed like a picket fence above the unsaturated triangular M3 dicationic center. Electrostatic interactions of the M(3+) units inside this cavity with the carboxylate anion RCO2(-) [R = tetraphenylporphyrinatozinc(II), ZnTPP; p-phenyltritolylporphyrinatozinc(II), ZnTTPP; p-phenyltritolylporphyrinatopalladium(II), PdTTPP] form dyads for through-space triplet energy transfers. The binding constants are on the order of 20,000 M(-1) in all six cases (298 K). The energy diagram built upon absorption and emission spectra at 298 and 77 K places the [Pt3(dppm)3(CO)](2+) and [Pd3(dppm)3(CO)](2+) as triplet energy donors, respectively, with respect to the ZnTPPCO2(-), ZnTTPPCO2(-), and PdTTPPCO2(-) pigments, which act as acceptors. Evidence for energy transfer is provided by the transient absorption spectra at 298 K, where triplet-triplet absorption bands of the metalloporphyrin chromophores are depicted at all time (at 298 K) with total absence of the charge-separated state in the nanosecond to microsecond time scale. Rates for energy transfer (ranging in the 10(4) s(-1) time scale) are extracted from the emission lifetimes of the [Pt3(dppm)3(CO)](2+) donor in the free chromophore and the host-guest assemblies. The emission intensity of [Pd3(dppm)3(CO)](2+) is too weak to measure its spectrum and emission lifetime in the presence of the strongly luminescent metalloporphyrin-containing materials. For the [Pd3(dppm)3(CO)](2+)...metalloporphyrin dyads, evidence for fluorescence and phosphorescence lifetime quenching of the porphyrin chromophore at 298 K is provided. These quenchings, exhibiting rates of 10(4) (triplet) and 10(8) s(-1) (singlet), are attributed to a photoinduced electron transfer from the metalloporphyrin to the cluster due to the low reduction potential.     

Succinimidinium N-sulfonic acid hydrogen sulfate as an efficient ionic liquid catalyst for the synthesis of 5-arylmethylene-pyrimidine-2,4,6-trione and pyrano[2,3-d]pyrimidinone derivatives

Research on Chemical Intermediates - Succinimidinium N-sulfonic acid hydrogen sulfate ([SuSA-H]HSO4) as a new ionic liquid is prepared and characterized using a variety of techniques, including...     

Lewis acid-promoted direct substitution of 2-methoxy-3-cyanopyridines by organo cuprates. Part 3: Facile preparation of nicotinamide and nicotinic acid derivatives

2-Methoxy-3-cyano-4,6-diarylpyridines were subjected to Lewis acid-promoted nucleophilic displacement reactions with various organo cuprates to afford the corresponding 2,4,6-trisubstituted nicotinonitriles. Subsequent hydrolysis of compounds 10 and 11 afforded the corresponding 2,4,6-trisubstituted nicotinic acid 22 and nicotinamide 23 derivatives, respectively. The mechanism of the displacement reaction has been studied experimentally and by molecular modeling calculations.     

High-performance liquid chromatographic stability indicating assay method of tianeptine sodium with simultaneous fluorescence and UV detection

The purpose of this work is to develop a sensitive, selective, and validated stability-indicating HPLC assay of tianeptine (TIA) in bulk drug and tablet form. TIA is subjected to different stress conditions, including UV-light, oxidation, acid base-base hydrolysis, and temperature. TIA and its possible degradation products are analyzed on Agilent-Zorbax-XDB-C18 column using gradient elution with acetonitrile and 0.02M sodium acetate (pH 4.2). The samples are monitored simultaneously with photo-diode array at 254 nm and fluoroscence detector set to 350 nm (ex) and 425 nm (em). TIA is integrated from its UV-chromatogram, and the photodecomposition products are integrated from the fluoroscence-chromatogram. TIA and its photodecomposition products are separated by TLC using ethyl acetate-n-hexane-glacial acetic acid-methanol (10.0:14.0:0.2:1.0, v/v) as developing system. One potential photodegradation product is detected by fluoroscence in TIA-tablet form and separated by TLC. The linear range of TIA is between 0.5 to 50 microg/injection with limits of quantitation and detection values of 30 and 8 ng/injection, respectively. The inter-assay percentage of deviation is not more than 0.03%, and the day-to-day variation is not more than 0.1%.     

Star‐Shaped Polyaromatic Ethers Coordinated to Redox‐Active Cyclopentadienyliron Moieties

This communication is focused on the controlled design of star‐shaped aromatic ethers with pendent cyclopentadienyliron moieties. A trimetallic core was prepared, which was then reacted with a number of oligomeric ether complexes to give star‐shaped polymers with six, nine, twelve and fifteen pendent cationic cyclopentadienyliron moieties. Cyclic voltammetric studies showed reduction of the iron centers between –0.99 and –1.41 V. Thermogravimetric analysis showed that loss of the metallic moieties occurred between 225 and 284°C.     

The reaction of 2‐amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]‐thiophene with diethyl malonate: synthesis of coumarin,pyridine, and thiazole derivatives

The reaction of 2‐amino‐3‐cyano‐4,5,6,7‐tetrahydrobenzo[b]thiophene ( 1 ) with diethyl malonate ( 2 ) gave two products: 3 and 4 . The reactivity of 3 toward a variety of chemical reagents was studied to give azoles, azines, and their fused derivatives. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:168–175, 2001     

Synthesis of substituted norbornenes and their polymerization to polynorbornenes with flexible aliphatic side‐chains

Synthesis and characterization of new thermally stable polynorbornenes functionalized with pendent flexible side‐chains are reported. The flexible side‐chains with terminal hydroxy groups were synthesized via S_NAr reactions of cyclopentadienyliron‐complexed chlorobenzenes with aliphatic diols. Condensation of these side‐chains with exo,endo‐5‐norbornene‐2‐carboxylic acid led to the formation of substituted monomers which were characterized using one‐ and two‐dimensional NMR techniques. Ring‐opening metathesis polymerization of these monomers yielded polynorbornenes with pendent side‐chains.