Determination of Anafranil in Pharmaceuticals by Difference and Difference-Derivative Spectrophotometry

Abstract

Difference (ΔA) and difference first- (ΔD1) and second- (ΔD2) derivative spectrophotometric methods are described for the assay and quality control of anafranil, a powerful antidepressant, in pharmaceutical formulations.

The procedures are based upon the measurement of ΔA, ΔD1 and ΔD2 of anafranil in alkaline solutions against their acidic solutions as blanks.

Interferences of the excipients and diluents or irrelevant absorptions are nullified. Calibration graphs of ΔA, ΔD1 and ΔD2 versus the concentration of the drug showed linear relationships up to 10 μg/ml, with correlation coefficients ranging from 0.9998 to 0.9999.

Detection limits at p = 0.01 level of significance were calculated to be 0.060 (ΔA), 0.056 (ΔD1) and 0.063 (ΔD2) μg/ml. The limits of quantification were 0.45 (ΔA), 0.36 (ΔD1) and 0.81 (ΔD2) μg/ml.

The procedures have been successfully applied to the determination of anafranil in synthetic samples and in commercial pills and injections for this drug with high reliability and repeatability.     

Utility of Derivative Spectrophotometry in the Determination of Carbochromen Hydrochloride and Dipyridamole in the Presence of Their Oxidative Degradation Products

Abstract

Direct spectrophotometric methods for the determination of carbochromen hydrochloride and dipyridamole, each in the presence of its oxidative degradation products, are presented. the methods are based on the first derivative (D₁) and second derivative (D₂) spectrophotometric measurement (absolute trough, U) at 336 nm and (Peak-trough, Y) at 309–342 nm for carbochromen hydrochloride and at 240–260 nm(U) and 246–268 nm(Y) for dipyridamole. Plots of D₁ or D₂ versus concentration were linear over the concentration range of 8.00–16.00 μg/ml for carbochromen hydrochloride and 4.00–12.00 μg/ml for dipyridamole. Oxidative degradation of these drugs has been optimized with respect to hydrogen peroxide concentration. Determining the intact in coexistence with its oxidative degradation product, the proposed derivative spectrophotometric methods proved to be of high potential in correcting the systematic error appearing in the results of the A_max method due to the latter. Assaying the commercial tablets, the proposed method gave results of high accuracy and reproducibility.     

A concise methodology for the synthesis of (−)-Δ-tetrahydrocannabinol and (−)-Δ-tetrahydrocannabivarin metabolites and their regiospecifically deuterated analogs

The availability of tetrahydrocannabinols (Δ⁹-THC), tetrahydrocannabivarins (Δ⁹-THCV), and their metabolites in both their undeuterated and deuterated forms is critical for the analysis of biological and toxicological samples. We report here a concise methodology for the syntheses of (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in significantly improved overall yields using commercially available starting materials. Our approach allowed us to obtain the key intermediates (6aR,10aR)-9-nor-9-oxo-hexahydrocannabinols in four steps from (+)-(1R)-nopinone. This was followed by an optimized Shapiro reaction to give the (−)-11-nor-9-carboxy-metabolites, which were converted to their respective (−)-11-hydroxy analogs. The synthetic sequence involves a minimum number of steps, avoids undesirable oxidative conditions, and incorporates the costly deuterated resorcinols near the end of the synthetic sequence. This methodology enabled us to synthesize eight regiospecifically deuterated (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in a preparative scale and high optical purity without deuterium scrambling or loss.     

In situ complexation of rhodium(II) tetracarboxylates with some derivatives of cysteine and related ligands studied by 1H and 13C nuclear magnetic resonance spectroscopy

The complexation of N-phthaloyl, N-formyl, and N,N-dimethyl derivatives of S-methylcysteine methyl ester (both racemic and optically pure) with three dimeric rhodium(II) salts, acetate Rh₂AcO₄, trifluoroacetate Rh₂TFA₄, and (R)-(+)-α-methoxy-α-trifluoromethylphenylacetate Rh₂Mosh₄ was investigated by nuclear magnetic resonance spectroscopy (NMR) at room and lower temperatures. The complexation was carried out in situ, in CDCl₃ solution using titration procedure; the results were examined by the analysis of ¹H and ¹³C NMR chemical shift change (Δδ). The complexation of free S-methyl cysteine and hydrochloride salt of its methyl ester was performed in D₂O solution. For comparison, complexation of some derivatives of leucine, phenylalanine, and proline was examined.

N-phthaloyl and N-formyl derivatives of cysteine formed 1 : 1 and 1 : 2 axial complexes with all dirhodium salts. Rhodium substrates were bonded via sulfur. In one case, the complexation of Rh₂TFA₄ by both sulfur and N-formyl oxygen was noted. Similar complexation of Rh₂TFA₄, via CHO group, was found for N-formyl derivatives of leucine, phenylalanine, and proline. For N,N-dimethyl derivative of cysteine, both N and S atoms were involved in bonding. At room temperature, in all cases, ligand exchange was fast on the NMR timescale.     

3-(4-β-D-吡喃阿洛糖苷-苯基)-4-芳基-5-芳基-1,2,4-噁二唑啉的合成及其镇静活性的研究

以豆腐果苷为原料, 与盐酸羟胺缩合反应生成4-β-D-吡喃阿洛糖苷-苯甲醛肟(2), 2与次氯酸叔丁酯发生取代反应生成4-β-D-吡喃阿洛糖苷-α-氯苯甲醛肟(3); 再将3与Schiff碱通过1,3-偶极环加成生成一系列3-(4-β-D-吡喃阿洛糖苷-苯基)-4-芳基-5-芳基-1,2,4-噁二唑啉(5a～5h). 3和 5a～5h共9个化合物均未见文献报道, 其结构经¹H NMR, IR和MS (HRMS)加以确认, 并对5a～5h进行了药理活性筛选. 结果表明, 部分化合物具有良好的镇静活性. 其中, 化合物5g (200, 100 mg•kg^－1)和5h (200, 100 mg•kg^－1)与豆腐果苷相比较具有更强的活性.     

Application of Difference and Derivative Ultraviolet Spectrometry for the Assay of Some Benzodiazepines

Abstract

Differential (δ A), second derivative (D₂) and differential second derivative (δ D₂) ultraviolet spectrophotometric methods have been described for the quantitiative estimation of clonazepam, diazepam and medazepam in pharmaceutical formulations such as drops, tablets and capsules. Interferences due to excipients and diluents are thereby avoided. Accuracy of the analyses with the proposed procedures is significantly greater than the conventional spectrophotometric and official methods.     

A Simple and Eco-Compatible One-Pot Synthesis of New Symmetrical Dithiocarbamate Podands and Their Dynamic NMR Studies

Abstract

A simple and eco-compatible synthesis of podands as 4_a-i is performed using amines (3_a-c ), CS₂, and dichlordiamides (DCDs) (2_{a, c} ) in the absence of a catalyst in water. Three reacting DCDs (2_a-c ) were obtained in the reaction of aromatic diamines (1_{a, c} ) with chloroacetyl chloride. Dynamic NMR spectroscopic data of three series of podands (4_a-c , 4_d-f , and 4_g-i ) are discussed and their free energies of activations are calculated (ΔG ^≠ _c s) at coalescence temperatures. The ΔG ^≠ _c of these podands were attributed to conformational isomerization in the range of 14.7–17 kcal/mol due to rotation and resonance effects about the thioamide C?N bond.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional figures.]     

地奥心血康中的两个新甾体皂苷

通过正相和反相硅胶柱层析, 从地奥心血康药粉的正丁醇萃取物中分离纯化出2个微量的新甾体皂苷, 通过MS和NMR(包括HMQC, HMBC和NOESY)等波谱解析, 结合化学降解分析将其结构鉴定为3β,26-二醇-25(R)-Δ^5,20(22)-二烯-呋甾-26-O-β-D-吡喃葡萄糖苷(1)和26-O-β-D-吡喃葡萄糖基-3β,20α,26-三醇-25(R)-Δ^5,22-二烯-呋甾-3-O-α-L-吡喃鼠李糖基(1→2)-[α-L-吡喃鼠李糖基(1→4)]-β-D-吡喃葡萄糖苷(2).     

NMR study of phase separation in D2O/ethanol solutions of poly(N-isopropylmethacrylamide) induced by solvent composition and temperature

¹H and ¹³C NMR spectroscopies were applied to investigate phase separation in solutions of poly(N-isopropylmethacrylamide) (PIPMAm) in D₂O/ethanol (EtOH) mixtures induced by solvent composition (cononsolvency) and temperature. Effects of EtOH content in D₂O/EtOH mixtures and temperature on the appearance and extent of the phase separation were characterized. Differences in mesoglobules formed during the phase separation induced by cononsolvency and temperature were found. For temperature-induced phase separation, ¹³C spin-spin relaxation times showed that besides the free EtOH expelled from the PIPMAm mesoglobules, there are also EtOH molecules bound in these mesoglobules. On the other hand, virtually no bound EtOH molecules were detected for mesoglobules formed as a consequence of the cononsolvency. For PIPMAm random copolymers containing negatively charged methacrylate units the phase separation induced by solvent composition was not observed.     

Crown-containing styryl dyes

Styryl dyes containing a crown ether group and a heteroaromatic moiety with a sulfoalkylN-substituent (1a,b) undergo photocyclodimerization in acetonitrile in the presence of Mg(ClO₄)₂ to give only the typeA isomer of cyclobutane derivative (2a,b). The photochemical regio- and stereoselectivity of the cycloaddition is explained by self-organization of thetrans-isomers of the styryl dyes upon complexation with the Mg²⁺ cations into dimers with a fixed mutual arrangement of multiple bonds.For part 7, see ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1449–1452, August, 1993.     

A new approach to the synthesis of cross-conjugated cyclopentenone prostaglandins. Synthesis of (±)-15-deoxy-Δ-prostaglandin J2 methyl ester

A new approach to 15-deoxy-Δ^12,14-prostaglandin J₂ and related structures based on the (±)-Corey lactone diol has been developed. The key stage of this approach involves building the structure of a prostaglandin (PG) derivative with leaving groups at positions 9, 13, and 15, followed by elimination of these groups by treatment with an organic base.     

The radiolysis of bromophenol blue in aqueous solutions

The effect of gamma radiation on the color intensity of aerated and oxygenated aqueous solution of bromophenol blue (BPB) was investigated. Ionizing radiation at increasing absorbed doses (D) brought about gradual bleaching (i.e. decrease in optical absorbance, -ΔA) of bromophenol blue solutions. The molar extinction coefficients of acidic, neutral, and alkaline solutions were measured and found to be independent of temperature during spectrophotometry between 20 and 40°C. Aerated and oxygen-saturated acidic solutions showed a linear response -ΔA vs D) up to doses of 2.4 and 2.1 kGy, respectively. Aerated alkaline solutions on the other hand showed a linear response up to 4.8 kGy. The decoloration yields for 5 × 10^-5 M bromophenol blue aqueous solutions, G(-BPB), obtained from the decrease in absorbance at 591 nm wavelength for acidic, neutral, and alkaline solutions, were 0.244, 0.113, and 0.098 (100 eV)^-1, respectively. The first-order rate constant for the reaction of OH radical with bromophenol, obtained from competition reactions with ethanol at pH 4, was found to be 9.1 +- 1.2 × 10⁹ M^-1 s^-1. The degree of decoloration of bromophenol blue in acidic solutions was found to decrease upon the addition of ethanol, G(-BPB) decreasing from 0.24 to 0.088 upon the addition of ethanol at a concentration of 10^-2M. Suggestions are made for possible radiation dosimetry in the dose range (0.1–5 kGy) by means of spectrophotometric analysis of absorption spectra.     

Abnormal Beckmann fragmentation/ring closing metathesis route for preparation of 18-nor-Delta-androgens and their 18-nor-13,17-epoxide derivatives

The synthesis of 18-nor-Δ¹³⁽¹⁷⁾-androgens and the structurally related 13,17-epoxides is described. The synthetic route involves the cleavage of 17-ketosteroids by an abnormal Beckmann rearrangement, modification of the D-ring cleavage product to obtain an intermediate tricyclic diene and ring closing metathesis of the diene to the 18-nor-Δ¹³⁽¹⁷⁾-androgen. (3α,5α)-18-Norandrost-13(17)-en-3-ol and the derivative 13α,17α- and 13β,17β-epoxides were prepared by this route.     

Application of Derivative and Ratio Spectra Derivative Spectrophotometry for the Determination of Pseudoephedrine Hydrochloride and Acrivastine in Capsules

Abstract

Two new spectrophotometric methods are used for the determination of acrivastine and pseudoephedrine hydochloride in their mixture without previous chemical separation. In the first, second derivative spectrophotometry, the measurements are made at 288.0 nm for acrivastine and at 270.2 nm for pseudoephedrine hydrochloride in the second derivative spectra of their solution in 0.1M NaOH. In the second, ratio spectra derivative spectrophotometry, the amplitudes are measured at 276.0 nm and 298.5 nm corresponding to two maximums for acrivastine, and at 252.6 nm and 268.3 nm corresponding to a maximum and a minumum, respectively, for pseudoephedrine hydrochloride in first derivative of their ratio spectra plotted by using of their solutions as divisor. The methods were successfully applied for the determination of these drugs in a commercial pharmaceutical formulation capsule.     

Chemical and Pharmacological Properties of 3-(Thiophen-2-yl)-4-substituted-Δ 2-1,2,4-triazoline-5-thiones

Three 3-(thiophen-2-yl)-4-substituted-Δ ² -1,2,4-triazoline-5-thiones were synthesized by intramolecular cyclization of 1-(thiophen-2-ylcarbonyl)-4-substituted thiosemicarbazides in alkaline medium. Their effects on the central nervous system (CNS) of mice in some behavioral tests were investigated. All investigated compounds displayed antinociceptive activity. The correlation between the structural features and bioactivity has been discussed.     

Antimicrobial Properties of 4-Aryl-3-(2-methyl-furan-3-yl)-Δ2-1,2,4-triazoline-5-thiones

Four 4-aryl-3-(2-methyl-furan-3-yl)-Δ²-1,2,4-triazole-5-thiones were synthesized by intramolecular cyclization of 4-aryl-1-[(2-methyl-furan-3-yl)carbonyl]thiosemicarbazides in alkaline medium. The antimicrobial activity of the synthesized triazoles was evaluated. Semiempirical calculations of geometries, energies, and QSAR parameters have been determined in the hope of gaining insight into different biological activities of closely related isomers. New RM1 parameterization has been shown to perform very well for this class of compounds.     

Metal chelates of ampicillin versus amoxicillin: synthesis,structural investigation,and biological studies

Solid chelates derived from some alkaline earth and transition metal complexes with ampicillin (Hamp, a) and amoxicillin (Hamox, b) were synthesized and characterized using elemental analysis, molar conductivity, IR, magnetic susceptibility, and thermogravimetric studies. Both drugs behave as tetradentate ligands coordinating to metal through amino, imino, and carboxylate as well as through β-lactamic carbonyl. All chelates have octahedral geometry except Cu(II) complexes which have square planar structure and uranium has pentagonal bipyramidal coordination. ¹H- and ¹³C-NMR of the Zn(II) and UO₂(VI) chelates are compared with the free ligands. The antimicrobial activity of the prepared chelates was determined.     

[2,2,2-TRIFLUOR-1-(2-HYDROXYPHENYL)ETHYL]-PHOSPHONSÄURE: MOLEKÜLSTRUKTUR VON [2,2,2-TRIFLUOR-1-(2-HYDROXYPHENYL)-ETHYL]DIMETHYLPHOSPHONAT

Abstract

The interaction of trimethylphosphite (1) and 2-trifluoroacetylphenol (2) yielded 4,5-benzo-2,2,2-trimethoxy-3-trifluoromethyl-1,2λ⁵[sgrave]⁵-oxaphosphol (3) and trimethylphosphate but not the expected 3-hydroxy derivative. Hydrolysis of compound 3 furnished the respective acyclic dimethylphosphonate 4 which was converted into the bis(trimethylsilyl)ester 5 and finally into the free phosphonic acid 6. O-trimethylsilylated compound 8 added to tris(trimethylsilyl)phospite (7) furnishing phosphonate 9 without abstracting the [sgrave]-oxygen. The molecular structure of 4 exhibited a somewhat distorted tetrahedral arrangement of substituents around phosphorus. An intermolecular hydrogen bridge O—H… O[dbnd]P was observed (O…O = 266.7 pm).     

SPECTROPHOTOMETRIC STUDY OF THE THERMODYNAMICS OF COMPLEXATION OF LITHIUM AND SODIUM IONS WITH DIBENZO-24-CROWN-8 IN BINARY DIMETHYLFORMAMIDE-ACETONITRILE MIXTURES USING MUREXIDE AS A METALLOCHROMIC INDICATOR

Abstract

Complexation of Li⁺ and Na⁺ with dibenzo-24-crown-8 has been studied in dimethylformamide-acetonitrile mixtures by means of a competitive spectrophotometric technique using murexide as metal ion indicator. Stabilities of the resulting 1:1 complexes were investigated at various temperatures and enthalpies and entropies of complexation were determined from the temperature dependence of the formation constants. Sodium forms a more stable complex with the crown ether than lithium. There is an inverse linear relationship between log K_f and the mole fraction of DMF in the solvent mixtures. The ΔH°-TΔS° plot of all thermodynamic data, obtained for both crown complexes in different solvent mixtures, shows a fairly good linear correlation, indicating the existence of an enthalpy-entropy compensation effect in complexation.     

Crown-ether styryl dyes

The surface enhanced Raman scattering (SERS) spectra of styryl dyes containing a crown-ether group and a heteroaromatic residue with sulfoalkyl (1a) or alkyl (1b)N-substituent and of their complexes with Mg²⁺ cations were recorded in the 10^–4–10^–8 mol L^–1 concentration range. A model for the interaction of compoundsla,b with a silver surface during their adsorption on an electrochemically treated electrode was suggested. Fastcis-trans relaxation of the adsorbed molecules1a,b and complexes (1a,b)Mg²⁺ was found. It was shown that at [1a] = 10^–5 mol L^–1 and moderate molar ratios (C _Mg/[1a] = 3/1 to 9/1) in acetonitrile solutions, (trans-1a)Mg²⁺ complexes are joined into head-to-tail type dimers. An excess of Mg²⁺ cations (C_Mg/[1a] > 100) leads to dissociation of the dimers yielding (trans-1a)(Mg²⁺)₂ complexes. The formation of dimers from complexes (trans-1a)Mg²⁺ is accompanied by a substantial distortion of the planar structure oftrans-1a. This may be an important factor influencing the efficiency of photocycloaddition involving dimers of (trans-1a)Mg²⁺.For part 15, see Ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2429–2436, December, 1995.The work was carried out with financial support of the Russian Foundation for Basic Research (Project No. 94-03-08760) and, to some extent, of INTAS (Grant No. 93-1829) and of the International Science Foundation (Grant No. MHAOOO).