Densitometry and indirect normal‐phase HPTLC–ESI–MS for separation and quantitation of drugs and their glucuronide metabolites from plasma

The present work describes novel methods using densitometry and indirect or off‐line high performance thin‐layer chromatography–mass spectrometry (HPTLC–MS) for the simultaneous detection and quantification of asenapine, propranolol and telmisartan and their phase II glucuronide metabolites. After chromatographic separation of the drugs and their metabolites the analytes were scraped, extracted in methanol and concentrated prior to mass spectrometric analysis. Different combinations of toluene and methanol–ethanol–n‐butanol–iso‐propanol were tested for analyte separation and the best results were obtained using toluene–methanol–ammonia (6.9:3.0:0.1, v/v/v) as the elution solvent. All of the drug–metabolite pairs were separated with a homologous retardation factor difference of ≥22. The conventional densitometric approach was also studied and the method performances were compared. Both of the approaches were validated following the International Conference on Harmonization guidelines, and applied to spiked human plasma samples. The major advantage of the TLC–MS approach is that it can provide much lower limits of detection (1.98–5.83 pg/band) and limit of quantitation (5.97–17.63 pg/band) with good precision (?3.0% coefficient of variation) compared with TLC–densitometry. The proposed indirect HPTLC–MS method is simple yet effective and has tremendous potential in the separation and quantitation of drugs and their metabolites from biological samples, especially for clinical studies.     

Determination of terbinafine in human plasma using UPLC–MS/MS: Application to a bioequivalence study in healthy subjects

A high‐throughput and sensitive ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method has been developed for the determination of terbinafine in human plasma. The method employed liquid–liquid extraction of terbinafine and terbinafine‐d7 (used as internal standard) from 100 μL human plasma with ethyl acetate–n‐hexane (80:20, v/v) solvent mixture. Chromatography was performed on a BEH C₁₈ (50 × 2.1 mm, 1.7 μm) column using acetonitrile–8.0 mm ammonium formate, pH 3.5 (85:15, v/v) under isocratic elution. For quantitative analysis, MS/MS ion transitions were monitored at m/z 292.2/141.1 and m/z 299.1/148.2 for terbinafine and terbinafine‐d7, respectively, using electrospray ionization in the positive mode. The method was validated according to regulatory guidance for selectivity, sensitivity, linearity, recovery, matrix effect, stability, dilution reliability and ruggedness with acceptable accuracy and precision. The method shows good linearity over the tested concentration range from 1.00 to 2000 ng/mL (r² ≥ 0.9984). The intra‐batch and inter‐batch precision (CV) was 1.8–3.2 and 2.1–4.5%, respectively. The method was successfully applied to a bioequivalence study with 250 mg terbinafine in 32 healthy subjects. The major advantage of this method includes higher sensitivity, small plasma volume for processing and a short analysis time.     

S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids: efficient organocatalysts for enantioselective sodium borohydride reductions of prochiral ketones

Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of (?)-menthol or (?)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthesized chiral ionic liquids have been characterized by ¹H, ¹³C NMR and Mass spectrometry. Moderate to excellent enantiomeric excess (ee > 99%) has been obtained in asymmetric sodium borohydride reduction of prochiral ketones using these salts as chiral catalysts.     

Thermal analysis of interaction between 2-PAM chloride and various excipients in some binary mixtures by TGA and DSC

Pralidoxime chloride known as 2-PAM chloride is used as antidote for nerve agent’s poisoning. This study was undertaken to establish the compatibility of 2-PAM chloride with a number of commonly used excipients by using thermoanalytical technique viz., differential scanning calorimetry (DSC) and thermogravimetry/differential thermogravimetry (TG/DTG) used in pharmaceutical formulation. The TG and DSC both results demonstrated that polyvinyl alcohol, polyacrylamide, microcrestline cellulose, hydroxypropyl cellulose, cellulose acetate, ethyl cellulose found to be compatible with 2-PAM chloride and chosen for the preparation of antidote against chemical warfare agents.     

A simple and cost-effective synthesis of sulfated β-cyclodextrin and its application as chiral mobile phase additive in the separation of cloperastine enantiomers

Journal of Inclusion Phenomena and Macrocyclic Chemistry - A simple and cost-effective method for the synthesis of sulfated β-cyclodextrin, one of the most widely used chiral mobile phase...     

Engaging thieno[2,3-b]indole-2,3-dione for the efficient synthesis of spiro[indoline-3,4′-thiopyrano[2,3-b]indole] by reaction with N-substituted isatilidenes

A simple and efficient method, proceeding through a new mechanistic pathway, for the synthesis of spiro[indoline-3,4-thiopyrano[2.3-b]indole derivatives have been developed by exploiting the reaction of thieno[2,3-b]indole-2,3-dione with N-substituted isatilidenes. The compounds synthesized have been screened for antibacterial activity. The generality of the reaction and mechanistic rationale are presented.     

Effect of precursor pH on structural,magnetic and catalytic properties of CoFe2O4@SiO2 green nanocatalyst

Research on Chemical Intermediates - Cobalt ferrite is a promising material for many therapeutic applications, photo-catalysis, gas detectors, high-density data storage, etc. Optimization of...     

Point‐of‐Care Amperometric Testing of Diabetic Marker (HbA1c) Using Specific Electroactive Antibodies

Specific immune detection of glycated hemoglobin is still a great challenge owing to the small epitopic difference between Hemoglobin (Hb) and HbA1c. We report a new electrochemical immunoassay format for point of care testing of HbA1c. A conducting self‐assembled monolayer of mercaptophenyl boronic acid (MPBA) was used as a capture layer for binding of glycated proteins and ferrocene tagged anti‐HbA1c antibody (FcAb) as a tracer molecule on a gold screen printed electrode. Validation of the new HbA1c assay was carried out using 6 clinical samples with known HPLC values and a correlation coefficient of 98 % was observed.