Preparation of amine-modified lignin and its applicability toward online micro-solid phase extraction of valsartan and losartan in urine samples.

In the present work, with the focus on an environmentally-friendly approach, some gels were prepared by synthesizing amine-modified lignin, extracted from sugarcane bagasse, and further esterification and subsequent freeze-drying. These lignin-based gels were implemented as extractive phases in an online micro-solid phase extraction (µSPE) setup in conjunction with high performance liquid chromatography (HPLC) with UV detector. The developed method was used for analytical determination of valsartan and losartan in urine samples. To study the effect of the functionalization process, the efficiency of the unmodified lignin and the functionalized lignin were compared both in the absence and the presence of graphene oxide (GO), presumably as a suitable doping agent. Surprisingly, higher extraction efficiency for the functionalized lignin, compared to both unmodified lignin and GO was observed. The amination process for the prepared gel was analyzed and proved by CHNS elemental analysis and Fourier transform infrared (FT-IR) spectroscopy. The morphology of sorbet was investigated via scanning electron microscope (SEM) imaging and a nanoscale cauliflower feature was observed. The method was optimized and subsequently applied to the analysis of the urine samples. Limits of detection (LOD) of 8 and 6 µg L - 1, limits of quantification (LOQ) of 27 and 20 µg L - 1 and linear dynamic range (LDR) of 27-2000 and 20-2000 µg L - 1 with intraday relative standard deviations (RSD%) of 4 and 3% were obtained for valsartan and losartan, respectively. The whole online µSPE-HPLC setup was conveniently used for the analysis of a patient urine sample and a quantity of 352 µg L - 1 of losartan was found. Acceptable relative recoveries (109-108 and 95-94% for valsartan and losartan) revealed the analytical potential of the method for the determination of drugs in complex urine samples.

Preparation of hollow porous molecularly imprinted and aluminum(III) doped silica nanospheres for extraction of the drugs valsartan and losartan prior to their quantitation by HPLC.

Water compatible hollow porous molecularly imprinted nanospheres (HP-MINs) have been prepared for specific recognition and extraction of the blood pressure regulating drugs valsartan (VAL) and losartan (LOS). All synthetic steps were performed in aqueous medium and without consumption of organic solvents. The morphology and functionality of the materials were characterized by FT-IR, FE-SEM, and TEM techniques. The adsorption and selectivity experiments demonstrate that the HP-MINs possess a high binding capacity, fast kinetics, excellent water dispersibility and remarkable selectivity for VAL and LOS. The HP-MINs were utilized for dispersive solid phase extraction of VAL and LOS prior to their determination by HPLC-UV. Main variables and their interactions on extraction yield were optimized by multivariate analysis with least amount of experiments. Under optimized conditions, the method has a linear response in the 5-2000 µg L-1 concentration range of both VAL and LOS. The limits of detection are 1.5 µg L-1 for VAL and 1.4 µg L-1 for LOS. Graphical abstract Schematic representation of dispersive solid phase extraction (d-SPE) of valsartan (VAL) and losartan (LOS) from urine sample by hollow porous molecularly imprinted nanospheres (HP-MINs).

Green-modified micellar liquid chromatography for isocratic isolation of some cardiovascular drugs with different polarities through experimental design approach.

Bilayer pseudo-stationary phase micellar liquid chromatography (MLC) was developed for simultaneous isocratic isolation of hydrochlorothiazide, as a basic-polar (hydrophilic) cardiovascular drug, as well as triamterene and losartan potassium, as acidic-nonpolar (hydrophobic) cardiovascular drugs. Utilizing a deep eutectic solvent (DES), as a novel green mobile phase additive in combination with acetonitrile (ACN) and acetic acid (ACA), drastically improved the chromatographic behavior of the drugs. Concentration of sodium dodecyl sulphate (SDS), as well as volume percentages of ACN, DES, and ACA were optimized by using a central composite design. The optimal composition of the mobile phase (0.12 mol L-1 SDS, 5% ACN, 4% DES, and 2% ACA) was chosen through the desirability function. The chromatographic peaks of both hydrophilic and hydrophobic drugs, respectively, emerged at high and low retention time values in the shortest total analysis time of 20 min (at a flow rate of 2 mL min-1). Analytical characterization of the developed approach was investigated through Food and Drug Administration (FDA) guidelines. Applicability of the method was evaluated by analysing of human plasma samples which were directly injected into the system.

Application of modified stir bar with nickel:zinc sulphide nanoparticles loaded on activated carbon as a sorbent for preconcentration of losartan and valsartan and their determination by high performance liquid chromatography.

In this study, the stir bar was coated for the first time with the ​nicel:zins sulphide nanoparticles (Ni:ZnS NPs) loaded on activated carbon (AC) (Ni:ZnS-AC) as well as 1-ethyl-3-methylimidazolium hexafluorophosphate ionic liquid (IL) using sol gel technique and was used for stir bar sorptive extraction (SBSE) of losartan (LOS) and valsartan (VAL) as the model compounds. The extracted analytes were then quantified by high performance liquid chromatography (HPLC) equipped with an ultra violet detector. The best extraction performance for LOS and VAL was obtained through the optimization of the parameters affecting SBSE including pH of sample solution, ionic strength, extraction time, volume of desorption solvent, desorption time, and stirring speed. The fractional factorial design (FFD) was used to find the most important parameters, which were then optimized by the central composite design (CCD) and the desirability function (DF). Under the optimal experimental conditions, wide linear ranges of 0.4-50µgL(-1) and 0.5-50µgL(-1) and good RSDs (at level of 5µgL(-1) and n=6) of 4.4 and 4.9% were obtained for LOS and VAL, respectively. With the enrichment factors (EFs) of 188.6 and 184.8-fold, the limits of detection (LODs, S/N=3) of the developed method were found to be 0.12 and 0.15µgL(-1) for LOS and VAL, respectively. The developed method was successfully applied to the determination of LOS and VAL in urine and plasma matrices.

Behavior of pharmaceuticals in waste water treatment plant in Japan.

The fate of pharmaceuticals in a wastewater treatment plant (WWTP) in Kumamoto, Japan with activated sludge treatment is reported. Selected pharmaceuticals were detected in influent. Results from the present study confirmed that Acetaminophen, Amoxicillin, Ampicillin and Famotidine were removed at a high rate (>90% efficiency). In contrast, removal efficiency of Ketoprofen, Losartan, Oseltamivir, Carbamazepine, and Diclofenac was relatively low (<50%). The selected pharmaceuticals were also detected in raw sludge. In digestive process, Indomethacin, Atenolol, Famotidine, Trimethoprim and Cyclofosamide were removed at a high (>70% efficiency). On the other hand, removal of Carbamazepine, Ketoprofen and Diclofenac was not efficient (<50%).

Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters.

ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.

Multi-syringe chromatography (MSC) system for the on-line solid-phase extraction and determination of hydrochlorothiazide and losartan potassium in superficial water, groundwater and wastewater outlet samples.

In this paper, a combination of multi-syringe chromatography analysis technique with extraction disks sorbents for the pre-concentration and determination of hydrochlorothiazide and losartan potassium in superficial water, groundwater and wastewater outlet samples has been developed. The system developed was proved for the determination of hydrochlorothiazide and losartan potassium in spiked water samples with recoveries ranging from 95 to 118%. The method involves the on-line enrichment of the targeted analytes from spiked water samples onto a Cation-SR sorbent material. The analytes are subsequently eluted and transported to the monolithic column, Chromolith Flash RP-18e column (25 mmx4.6 mm i.d.). The mobile phase used was 10 mM potassium dihydrogen phosphate (pH 3.0):acetonitrile:methanol (60:30:10 v/v/v), flow-rate 0.8 mL min(-1). UV detection is carried out at 226 nm. Under the optimized chemical and physical variables, the detection limit for hydrochlorothiazide and losartan potassium calculated as 3Syx/b was 0.07 and 0.09 mgL(-1), respectively, for a sample loading volume of 1.0 mL.

Simultaneous determination of hydrochlorothiazide and losartan potassium in tablets by high-performance low-pressure chromatography using a multi-syringe burette coupled to a monolithic column.

This contribution describes use of a separation method based on on-line coupling of a multisyringe flow system with a chromatographic monolithic column for simultaneous determination of hydrochlorothiazide and losartan potassium in tablets. The system comprised a multisyringe module, three low-pressure solenoid valves, a monolithic C(18) column (25 mm x 4.6 mm i.d.), and a diode-array detector. The mobile phase was 10 mmol L(-1) potassium dihydrogen phosphate (pH 3.1)-acetonitrile-methanol (65:33:2 v/v/v) at a flow rate 0.8 mL min(-1). UV detection was carried out at 226 nm. The multi-syringe chromatographic (MSC) method with UV spectrophotometric detection was optimized and validated. Results from validation were very good. The analysis time was about 400 s. The method was found to be applicable to routine analysis of both compounds in tablets. The coupling of the monolithic columns with a multi-syringe flow-injection analysis manifold provides an excellent and inexpensive tool to solve the separation problems without use of HPLC instrumentation.

[Isolation and purification of the process impurity in losartan by reversed-phase column chromatography].

A process impurity (approximately 4%, w/w) was isolated from losartan crude by low-pressure reversed-phase column chromatography. At first the elution portions containing the target compound were collected. After evaporation and recrystallization, the purity of the target compound was found to be over 99% based on high performance liquid chromatography with ultraviolet absorption. The electrospray ionization-mass spectrometry result showed that it was an isomeric compound of losartan, which had same fragmentation pattern with its parent compound. And at last the compound was further characterized by nuclear magnetic resonance. This research demonstrates that the low-pressure reversed-phase column chromatography can raise separation efficiency and recovery comparing with other conventional column chromatography, and the technique can be applied as an effective means for the enrichment and extraction of impurities in pharmaceutical separation.