Sequential hollow-fiber liquid phase microextraction for the determination of rosiglitazone and metformin hydrochloride (anti-diabetic drugs) in biological fluids.

A new analytical method for the simultaneous determination of the antidiabetic drugs rosiglitazone (ROS) and metformin hydrochloride (MH) with marked differences in their affinity towards organic solvents (log P of 2.4 and -1.43, respectively) was developed. Prior to the HPLC separation, the drugs were subjected to a sequential hollow fiber liquid phase microextraction (HF-LPME) procedure. Two sequential HF-LPME approaches were considered, the preferred one involves the use of two vials containing solution mixtures for the extraction of ROS (vial 1) and MH (vial 2), respectively, but using the same fiber and acceptor phase. Important parameters that affect the extraction efficiency such as extracting solvent, donor phase conditions, HCl concentration, agitation, extraction time, addition of salt, etc. were studied. Under the optimum conditions, good enrichment factors (EF, 471 and 86.6 for ROS and MH, respectively) were achieved. Calibration curves were linear over the range 1-500 (r(2)=0.998) and 5-2500 ng mL(-1) (r(2)=0.999) for ROS and MH, respectively. The relative standard deviation values (RSD%) for six replicates were below 8.4%. Detection and quantitation limits based on S/N ratio of 3 and 10 were 0.12, 1.0 and 0.36, 3.0 ng mL(-1) for ROS and MH, respectively. The proposed method is simple, sensitive and opens up new opportunities for the microextraction of analytes with contrasting properties.

Hollow fiber liquid phase microextraction with in situ derivatization for the determination of trace amounts of metformin hydrochloride (anti-diabetic drug) in biological fluids.

A three phase hollow fiber liquid-phase microextraction with in situ derivatization (in situ HF-LPME) followed by high-performance liquid chromatography-ultraviolet detection (HPLC-UV) method was developed for the trace determination of metformin hydrochloride (MH) in biological fluids. A new derivatization agent pentafluorobenzoyl chloride (PFBC) was used. Several parameters that affect the derivatization and extraction efficiency were studied and optimized (i.e., type of organic solvent, volume of NaOH (4M) and derivatization agent in the donor phase, acceptor phase (HCl) concentration, stirring speed, temperature, time and salt addition). Under the optimum conditions (organic solvent, dihexyl ether; volume of NaOH (4M) and derivatization agent (10mg PFBC in 1mL acetonitrile) in the donor phase, 600 and100µL, respectively; acceptor phase, 100mM HCl (10µL); stirring speed, 300rpm; extraction time, 30min; derivatization temperature, 70°C; without addition of salt) an enrichment factor of 210-fold was achieved. Good linearity was observed over the range of 1-1000ngmL(-1) (r(2)=0.9998). The limits of detection and quantitation were 0.56 and 1.68ngmL(-1), respectively. The proposed method has been applied for the determination of MH in biological fluids (plasma and urine) and water samples. Prior to the microextraction treatment of plasma samples, deproteinization step using acetonitrile was conducted. The proposed method is simple, rapid, sensitive and suitable for the determination of MH in a variety of samples.

Investigation of crystal structure influence on spectroscopic and photoluminescent properties of terbium-picrate triethylene glycol complex.

The [Tb(Pic)(2)(H(2)O)(EO3)](Pic)·0.5(EO3) complex, for which EO3 and Pic stand for triethylene glycol and picrate anion, respectively, was successfully prepared and characterized. The Tb(III) complex was crystallized in triclinic structure with space group P1¯. The Tb(III) ion was coordinated to nine oxygen atoms from one EO3 ligand, one water molecule, and two Pic anions. The photoluminescent (PL) spectrum of the complex displayed characteristic narrow bands arising from intraconfigurational transitions of the Tb(III) ion. The strongest emission was centred at 544 nm ((5)D(4)→(7)F(5)), which was responsible for the green emission. The short acyclic chain length of the EO3 ligand, lanthanide contraction, and a bulky picrate anion affected the PL intensity, coordination environment around the Tb(III) ion, and crystal structure of the inner-sphere [Tb(Pic)(2)(H(2)O)(EO3)](+) moiety. The unique crystal structure in the Tb complex contained a half mole of triethylene glycol solvated. The complex had a high thermal stability due to the role of π-π stacking interactions of the Pic anions. The appearance of an emission from the ligands suggests that the photoluminescence of ligands cannot be quenched by coordination to the Tb(III) ion in its complex, so the intramolecular energy transfer process from the triplet state of the ligands (T(1)(L)) to the resonant emissive energy level of Tb(III) is not effective.

A 4-hydroxy-N'-[(E)-(2-hydroxyphenyl)methylidene]benzohydrazide-based sorbent material for the extraction-HPLC determination of biogenic amines in food samples.

A sorbent material based on a newly synthesized hydrazone ligand, 4-hydroxy-N'-[(E)-(2-hydroxyphenyl)methylidene]benzohydrazide was prepared by immobilizing the ligand into a silica sol-gel matrix. The capability of the sorbent material for the extraction of seven biogenic amines (BAs), i.e., tryptamine (TRY), beta-phenylethylamine (PEA), putrescine (PUT), cadaverine (CAD), histamine (HIS), tyramine (TYR), and spermidine (SPD) was studied. Under the adopted conditions, the sorbent showed good selectivity towards PUT, CAD, HIS and SPD (% extraction (%E)>96) while %E for TYR, TRY and PEA were 82.0, 78.9 and 46.4%, respectively. The sorbent could be used up to six extraction cycles for SPD, CAD and PUT and was applied to the determination of food samples ("budu", ketchup, orange juice, soy sauce) that were spiked with 20 mg L(-1) of the BAs. The extracted analytes were derivatized with dansyl chloride before the HPLC determination. With the exception of HIS and TYR in "budu" sample, reasonable recoveries were found for the other analytes in all the tested food samples.

Determination of underivatized long chain fatty acids using RP-HPLC with capacitively coupled contactless conductivity detection.

A reversed-phase high-performance liquid chromatographic method with capacitively coupled contactless conductivity detector (C(4)D) has been developed for the separation and the simultaneous determination of five underivatized long chain fatty acids (FAs), namely myristic, palmitic, stearic, oleic, and linoleic acids. An isocratic elution mode using methanol/1mM sodium acetate (78:22, v/v) as mobile phase with a flow rate of 0.6 mL min(-1) was used. The separation was effected by using a Hypersil ODS C(18) analytical column (250 mm x 4.6 mm x 5 microm) and was operated at 45 degrees C. Calibration curves of the five FAs were well correlated (r(2)>0.999) within the range of 5- 200 microg mL(-1) for stearic acid, and 2-200 microg mL(-1) for the other FAs. The proposed method was tested on four vegetable oils, i.e., pumpkin, soybean, rice bran and palm olein oils; good agreement was found with the standard gas chromatographic (GC) method. The proposed method offers distinct advantages over the official GC method, especially in terms of simplicity, faster separation times and sensitivity.

Extraction of biogenic amines using sorbent materials containing immobilized crown ethers.

Three sorbent materials (A18C6-MS, DA18C6-MS and AB18C6-MS) based on the crown ether ligands, 1-aza-18-crown-6, 1,4,10,13-tetraoxa-7,16-diazacyclo octadecane and 4'-aminobenzo-18-crown-6, respectively, were prepared by the chemical immobilization of the ligand onto mesoporous silica support. The sorbents were characterized by FT-IR, scanning electron microscopy-energy dispersive X-ray microanalysis, elemental analysis and nitrogen adsorption-desorption test. The applicability of the sorbents for the extraction of biogenic amines by the batch sorption method was extensively studied and evaluated as a function of pH, biogenic amines concentration, contact time and reusability. Under the optimized conditions, all the sorbents exhibited highest selectivity toward spermidine (SPD) compared to other biogenic amines (tryptamine, putrescine, histamine and tyramine). Among the sorbents, AB18C6-MS offer the highest capacity and best selectivity towards SPD in the presence of other biogenic amines. The AB18C6-MS sorbent can be repeatedly used three times as there was no significant degradation in the extraction of the biogenic amines (%E>85). The optimized procedure was successfully applied for the separation of SPD in food samples prior to the reversed-phase high performance liquid chromatography separation.

In situ derivatization hollow fibre liquid-phase microextraction for the determination of biogenic amines in food samples.

Hollow fibre liquid-phase microextraction with in situ derivatization using dansyl chloride has been successfully developed for the high-performance liquid chromatography-ultraviolet (HPLC-UV) determination of the biogenic amines (tryptamine, putrescine, cadaverine, histamine, tyramine, spermidine) in food samples. Parameters affecting the performance of the in situ derivatization process such as type of extraction solvent, temperature, extraction time, stirring speed and salt addition were studied and optimized. Under the optimized conditions (extraction solvent, dihexyl ether; acceptor phase, 0.1M HCl; extraction time, 30 min; extraction temperature, 26 degrees C; without addition of salt), enrichment factors varying from 47 to 456 were achieved. Good linearity of the analytes was obtained over a concentration range of 0.1-5 microg mL(-1) (with correlation coefficients of 0.9901-0.9974). The limits of detection and quantification based on a signal-to-noise ratio of 3-10, ranged from 0.0075 to 0.030 microg mL(-1) and 0.03 to 0.10 microg mL(-1), respectively. The relative standard deviations based on the peak areas for six replicate analysis of water spiked with 0.5 microg mL(-1) of each biogenic amine were lower than 7.5%. The method was successfully applied to shrimp sauce and tomato ketchup samples, offering an interesting alternative to liquid-liquid extraction and solid phase extraction for the analysis of biogenic amines in food samples.

Coordination of Ce(III) and Nd(III) with pentaethylene glycol in the presence of picrate anion: spectroscopic and X-ray structural studies.

(1)H NMR evidence for direct coordination between the Ln(III) ion and the oxygen atoms of the pentaethylene glycol (EO5) ligand and the picrate anion (Pic) in [Ln(Pic)(2)(EO5)][Pic] {Ln=Ce and Nd} complexes are confirmed by single X-ray diffraction. No dissociation of Ln-O bonds in dimethyl sulfoxide-d solution was observed in NMR studies conducted at different temperatures ranging 25-100 degrees C. The Ln(III) ion was chelated to nine oxygen atoms from the EO5 ligand in a hexadentate manner and the two Pic anions in each bidentate and monodentate modes. Both compounds are isostructural and crystallized in monoclinic with space group P2(1)/c. Coordination environment around the Ce1 and Nd1 atoms can be described as tricapped trigonal prismatic and monocapped square antiprismatic geometries, respectively. The crystal packing of the complexes have stabilized by one dimensional (1D) chains along the [001] direction to form intermolecular O-Hcdots, three dots, centeredO and C-Hcdots, three dots, centeredO hydrogen bonding. The molar conductance of the complexes in DMSO solution indicated that both compounds are ionic. The complexes had a good thermal stability. Under the UV-excitation, these complexes exhibited the red-shift emission.

Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis.

A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either beta-cyclodextrin (beta-CD) or 18-crown-6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over beta-CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R(s)) in the range of 2-4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra- and inter-day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed.

Enantioselective analysis of primaquine and its impurity quinocide by capillary electrophoresis.

A capillary electrophoretic (CE) method for the baseline separation of the enantiomers of primaquine diphosphate (PQ) and quinocide (QC) (a major contaminant) in pharmaceutical formulations is proposed. Both components were separated under the following conditions: 50 mm tris phosphate buffer (pH 3.0) containing 15 mm hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as background electrolyte; applied voltage, 16 kV; capillary temperature, 25 degrees C; detection wavelength, 254 nm; hydrostatic injection, 10 s. The separations were conducted using a 35 cm length and 50 microm i.d. uncoated fused silica capillary column. Under the optimized conditions, the components were successfully separated in about 5 min. Intraday precision of migration time and corrected peak areas when expressed as relative standard deviation ranged from 0.17 to 0.45 and 2.60 to 3.94%, respectively, while the interday precision ranged from 2.59 to 4.20 and 3.15 to 4.21%, respectively. After the validation exercise, the proposed method was applied for the determination of QC impurity in PQ formulations.

Development of a capillary electrophoresis method for the enantioselective estimation of primaquine in pharmaceutical formulations.

A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).

Aqua-dipicrato(tetra-ethyl-ene glycol)gadolinium(III) picrate methanol hemisolvate.

THE ASYMMETRIC UNIT OF THE TITLE COMPOUND [SYSTEMATIC NAME: aqua-bis(2,4,6-trinitro-phenolato)(3,6,9-trioxaundecane-1,11-diol)gadolinium(III) 2,4,6-trinitro-phenolate methanol hemi-solvate], [Gd(C(6)H(2)N(3)O(7))(2)(C(8)H(18)O(5))(H(2)O)](C(6)H(2)N(3)O(7))·0.5CH(4)O, contains two crystallographically independent Gd(III) complex cations with two uncoordinated picrate anions and one methanol mol-ecule. Each Gd(III) atom has nine coordination sites occupied by five O atoms of tetra-ethyl-ene glycol as a penta-dentate ligand, one O atom of a water mol-ecule and three O atoms of the two picrate anions as bidentate and monodentate ligands. The geometry is distorted tricapped trigonal prismatic. The mean planes of the two coordinated mono- and bidentate picrate ligands to the Gd(III) center are almost perpendicular to each other, as indicated by the dihedral angles of 89.92 (8) and 86.60 (8)° in the two complex cations. The ions are arranged in a two-dimensional network parallel to the ac plane. Short O⋯O and N⋯O contacts between the nitro groups, intra-molecular C-H⋯O hydrogen bonds, inter-molecular O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds, and two π-π inter-actions between benzene rings [centroid-centroid distances = 3.8073 (10)-3.9831 (10) Å] are observed. The methanol solvent mol-ecule is disordered over two positions, with site-occupancy factors of ca 0.6 and 0.4.

Dibenzo-18-crown-6-picric acid-water (1/2/3).

In the crown ether ring of the title compound, C(20)H(24)O(6)·2C(6)H(3)N(3)O(7)·3H(2)O, the O-C(H(2))-C(H(2))-O torsion angles indicate a gauche conformation of the ethyl-eneoxy units, while the C-O-C-C torsion angles indicate planarity of these segments; the dihedral angle between the two benzene rings is 44.53 (13)°. In both picric acid mol-ecules, one of the nitro groups is twisted away from the attached ring. The mol-ecules are linked into chains along the b axis via inter-molecular O-H⋯O hydrogen bonds. In addition, the crystal structure is stabilized by C-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance between benzene rings = 3.5697 (16) Å].

Tris(nitrato-κO,O')bis-(1,10-phenanthroline-κN,N')holmium(III).

In the title compound, [Ho(NO(3))(3)(C(12)H(8)N(2))(2)], the ten-coordinate Ho(III) ion is chelated by four N atoms from two phenanthroline (phen) ligands and six O atoms from three bidentate nitrate groups. The environment around the Ho atom can be described as a distorted bicapped square anti-prism. Two phenanthroline ligands form a dihedral angle of 43.72 (13)°. Short inter-molecular distances between the centroids of the six-membered rings [3.6887 (14)-3.8374 (16) Å] indicate the existence of π-π inter-actions, which link the mol-ecules into stacks extended in the [10] direction. The crystal packing is further stabilized by weak inter-molecular C-H⋯O hydrogen bonds.

Flow injection determination of anisidine value in palm oil samples using a triiodide potentiometric detector.

A flow injection analysis (FIA) procedure for the determination of anisidine value (AV) in palm olein using a triiodide detector is described. Undiluted oil sample and chloramine-T reagent were added to a reaction chamber, and reaction was accelerated by applying a short vortex action (typically for 30 s). After allowing the emulsified oil phase to be separated from the aqueous phase (bottom layer), an aliquot of the aqueous phase (containing unreacted chloramine-T) was aspirated into a carrier stream that contained I(-) where the chloramine-T oxidized the I- to form I3(-) which was finally detected by a flow-through triiodide potentiometric detector. Variables that affect the FIA signals such as size of the reaction chamber, oil and reagent flow rates, chloramine-T concentration, vortex time, time for phase separation, carrier stream pH and injected volume were studied. The optimized FIA procedure is linear over 1.0-23.0 AV. The method exhibits good repeatabililty (R.S.D. of +/-3.16% (n = 4) for the determination of 5.0 AV) and a sampling rate of 40 samples per hour was achieved. Good correlation (r2 = 0.996 (n = 4)) between the proposed method and the manual American Oil Chemists' Society procedure was found when applied to the determination of twenty different types of palm olein samples.

Sequential flow injection determination of chlorine species using a triiodide-selective electrode detector.

A flow injection analysis (FIA) method for the determination of four residual chlorine species, namely combined available chlorine (CAC), free available chlorine (FAC), total available chlorine (TAC) and chlorite (ClO2-) was developed using a flow-through triiodide-selective electrode as a detector. An important strategy of speciation studies utilized the kinetic discrimination of reactions between the CAC and FAC with Fe2+, which was applied to the speciation of FAC, CAC and TAC. The speciation of available chlorine species and chlorite (an oxychlorine species) was achieved by using the same set-up, but using flow streams of different pH. The effects of the pH of the carrier stream, the flow rate and the sample volume were studied. The method exhibited linearity from 2.8 x 10(-6) to 2.8 x 10(-4) M active chlorine (expressed as OCl-) with a detection limit of 1.4 x 10(-6) M. The selectivity of the method was studied by examining the minimum pH for the oxidation of iodide by other oxidants, and also by assessing the potentiometric selectivity coefficients. The proposed method was successfully applied to the determination of chlorine species in tap water, and disinfecting formulations where good agreement occurred between the proposed and standard methods were found.

Flow-through chloroquine sensor and its applications in pharmaceutical analysis.

Poly (vinyl chloride) membrane electrodes that responded selectively towards the antimalarial drug chloroquine are described. The electrodes were based on the use of the lipophilic potassium tetrakis(4-chlorophenyl)borate as ion-exchanger and bis(2-ethylhexyl)adipate (BEHA), or trioctylphosphate (TOP) or dioctylphenylphosphonate (DOPP) as plasticizing solvent mediator. All electrodes produced good quality characteristics such as Nernstian- and rapid responses, and are minimally interfered with by the alkali and alkaline earth metal ions tested. The membranes were next applied to a flow-through device, enabling it to function as flow-injection analysis (FIA) detector. The performance of the sensor after undergoing the FIA optimization was further evaluated for its selectivity characteristics and lifetime. Results for the determination of chloroquine in synthetic samples that contained common tablet excipients such as glucose, starch, and cellulose, and other foreign species such as cations, citric acid or lactic acid were generally satisfactory. The sensor was also successfully used for the determination of the active ingredients in mock tablets, synthetic fluids and biological fluids. The sensor was applied for the determination of active ingredients and the dissolution profile of commercial tablets was also established.

Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography.

A reversed-phased HPLC method that allows the separation and simultaneous determination of the preservatives benzoic (BA) and sorbic acids (SA), methyl- (MP) and propylparabens (PP) is described. The separations were effected by using an initial mobile phase of methanol-acetate buffer (pH 4.4) (35:65) to elute BA, SA and MP and changing the mobile phase composition to methanol-acetate buffer (pH 4.4) (50:50) thereafter. The detector wavelength was set at 254 nm. Under these conditions, separation of the four components was achieved in less than 23 min. Analytical characteristics of the separation such as limit of detection, limit of quantification, linear range and reproducibility were evaluated. The developed method was applied to the determination of 67 foodstuffs (mainly imported), comprising soft drinks, jams, sauces, canned fruits/vegetables, dried vegetables/fruits and others. The range of preservatives found were from not detected (nd)--1260, nd--1390, nd--44.8 and nd--221 mg kg(-1) for BA, SA, MP and PP, respectively.