Hydrothermal treatment of microcrystalline cellulose under mild conditions: characterization of solid and liquid-phase products

Microcrystalline cellulose (MCC) particles were subjected to hydrothermal treatment using an autoclave with temperatures ranging from 200 to 250 °C and reaction times ranging from 20 to 100 min. The structure and chemical composition of the reacted solid phase was analyzed by X-ray diffraction, thermo-gravimetric analysis, FTIR spectroscopy and ¹³C-NMR spectroscopy. The relative composition of the water-soluble products was determined by one-dimensional ¹H-NMR and two-dimensional homo and hetero-nuclear NMR spectroscopy. Within the experimental temperature and treatment time ranges, the crystallinity of the reacted solid phase was found to be mostly dependent on the treatment temperature while the aqueous solution was found to change with both temperature and treatment time. At the maximum temperature employed in this study (250 °C), the solid products are similar to amorphous oxidized carbon with glucose as the main water-soluble product. At lower temperatures the particles are unconverted MCC and the liquid products are primarily levulinic acid, formic acid and acetic acid with smaller quantities of 5-hydroxymethyl-furfural and glucose. Heterogeneous and liquid phase reaction-schemes are proposed to explain the observed solid and water-soluble products as a function of temperature and treatment time.     

Solid phase radioimmunoassay for testosterone in human serum using antibodies coupled to magnetizable cellulose

Summary A simple user-friendly, solid phase radioimmunoassay for testosterone in human serum based on magnetic particles is described. IgG fractions precipitated from polyclonal testosterone antiserum were coupled to magnetizable cellulose particles using carbonyl diimidazole. The prepared antibody solid phase was stable for one year when stored at 4 °C. The optimized assay involves the incubation of 50 ml of testosterone standards (0.3-10 ng/ml), 100 ml of magnetizable cellulose particle coupled antibody suspension and 100 ml of ¹²⁵I-testosterone derivative for 4 hours at 37 °C. At the end of the incubation, the tubes were placed on a magnetic rack for 10 minutes after the addition of wash buffer and decanted. The sensitivity of the assay is 0.2 ng/ml. The intra-assay variation was <15% throughout the assay range. The recovery varied from 88 to 115%. On dilution of samples having high levels of testosterone, linearity ranged between 87 and 125%. Correlation coefficient of 0.978 was obtained when the developed solid phase assay was compared to the earlier established liquid phase assay.     

The role of cations in homogeneous succinoylation of mulberry wood cellulose in salt-containing solvents under mild conditions

The role of two cations [tetraethylammonium⁺ (TEA⁺) and tetrabutylammonium⁺ (TBA⁺)] in the homogeneous succinoylation of mulberry wood (MW) cellulose in dimethyl sulfoxide (DMSO)/tetraethylammonium chloride (TEACl) and DMSO/tetrabutylammonium fluoride (TBAF) was investigated using the intrinsic viscosity and two-dimensional nuclear Overhauser effect NMR spectroscopy (2D NOESY). The intrinsic viscosity of MW cellulose solution strongly depends on the salt dosage for both TEACl and TBAF, indicating that the increase in the hydrodynamic size of cellulose chains was caused by the interactions between salts and cellulose, which promotes the solvation process of cellulose in solution. Two-dimensional NOESY spectra reveal that cations bind to cellobiose in DMSO by the interactions between α-methylene groups of TEA⁺ (or TBA⁺) and C1/C1′ groups of cellobiose, and the intensities of the respective crosspeaks increase with increasing TEACl dosage from 5 to 10 mg/ml, but no change was present with TBAF at the same concentration range. Taking cellobiose as a model compound for cellulose, it can be expected that TEA⁺ (or TBA⁺) and cellulose form polyelectrolyte-like complexes. The degree of substitution (DS) of homogeneous succinoylation of MW cellulose benefits from the interactions between TEA⁺ (or TBA⁺) and cellulose evidenced by FT-IR spectra and CP/MAS ¹³C NMR spectra. The DS of the succinylated cellulose declines at TBAF concentrations higher than 11 wt% probably because of the steric hindrance effects of TBA⁺.     

Characterization of chitosan microparticles reinforced cellulose biocomposite sponges regenerated from ionic liquid

The chitosan-microparticles reinforced cellulose biocomposite sponges regenerated from ionic liquid were prepared and characterized. Fourier transform infrared (FTIR) spectroscopy confirmed that the cellulose dissolved in 1-allyl-3-methylimidazolium chloride without derivatization. Chitosan particles as reinforcement were incorporated into the cellulose matrix. FTIR spectra indicated hydrogen bonding between hydroxyl groups of cellulose and chitosan. The biocomposite sponges showed uniform three-dimensional interconnected porous structures. The breaking strength of the sponges increased significantly, from 0.09 to 0.32 MPa with the addition of 1.0 wt% chitosan. The sponges also demonstrated excellent antibacterial activity against S. aureus and E. coli with the average inhibition zone diameters >2 mm and the inhibition rate higher than 80 %. Furthermore, the biocomposite sponges exhibited good moisture penetrability and high porosity. The water uptake ability of the sponge was >25 times of its weight in water with a fast swelling. The chitosan/cellulose composite sponge is expected to be a promising material for potential applications as wound dressing.     

Interactions of collagen and cellulose in their blends with 1-ethyl-3-methylimidazolium acetate as solvent

Collagen/cellulose blended solutions with collagen/cellulose mass ratio (Col/Cel) of 0, 1/40, 1/20, 1/10 and 1/5 were prepared using [Emim]Ac as solvent. The interactions between the two polymers before and after regeneration were investigated. In steady shear flow, all of the experimental viscosity values were greater than those of the estimated values calculated from the log-additivity rule for each sample, suggesting interactions between the two polymers in solutions. All solutions exhibited shear thinning behavior and the flow curves could be described by Cross model. Zero shear viscosity (η ₀) versus Col/Cel was examined and a linear increase (from 8.73 to 16.39 Pa·s) can be observed for η ₀ as Col/Cel ≤ 1/10, while there was only a slight increase (from 16.39 to 18.42 Pa·s) in η ₀ as Col/Cel increased to 1/5. Dynamic rheology results suggested the existence of aggregates in solution with Col/Cel = 1/10. Furthermore, the activation energy of solution was 84.5 kJ mol^?1 as Col/Cel = 1/10, higher than that of cellulose solution (44.2 kJ mol^?1). Regenerated films were prepared and characterized to trace back the interactions between the two polymers in [Emim]Ac. Fourier transform infrared spectroscopy indicated the hydrogen-bond interaction between collagen and cellulose in films. The denaturation temperature of collagen in films with Col/Cel ≤ 1/10 could be improved, but it was decreased with the increase of collagen content, and finally was reduced to be close to that of collagen as Col/Cel = 1/5. The features of dynamic mechanical analysis for films were indicative of the lack of homogeneity between collagen and cellulose as Col/Cel = 1/5. Atomic force microscopy images further confirmed the phase-separation when Col/Cel = 1/5.     

Ion beam irradiation of ZnS dispersed in PMMA and its photocatalytic application

ZnS nanoparticles implanted with 45 keV O⁵⁺ ion beam exhibited 83.6 % degradation of methyl blue in 2 h. This idea was utilized to fabricate nanocomposite system of ZnS and PMMA where ZnS nanoparticles were immobilized in PMMA film and irradiated with 45 keV O⁵⁺ ion beam at particle fluence of 2.5 × 10¹⁵, 1 × 10¹⁶ and 4 × 10¹⁶ particles/cm². These irradiated batches of ZnS nanoparticle immobilized in PMMA batches revealed formation of porous structure characterized by scanning electron microscopy and these batches exhibited 54 % photocatalytic degradation of methyl blue in 80 min which was higher as compared to the pristine ZnS nanoparticles.     

The Development and Validation of a Stability-Indicating UHPLC-DAD Method for Determination of Perindopril l-Arginine in Bulk Substance and Pharmaceutical Dosage Form

A stability-indicating ultra-high-performance liquid chromatography (UHPLC) method with a diode array detector was developed and validated for the determination of cis/trans isomers of perindopril l-arginine in bulk substance and pharmaceutical dosage form. The separation was achieved on a Poroshell 120 Hilic (4.6 × 150 mm, 2.7 µm) column using a mobile phase composed of acetonitrile–0.1 % formic acid (20:80 v/v) at a flow rate of 1 mL min^?1. The injection volume was 5.0 µL and the wavelength of detection was controlled at 230 nm. The selectivity of the UHPLC-DAD method was confirmed by determining perindopril l-arginine in the presence of degradation products formed during acid–base hydrolysis and oxidation as well as degradation in the solid state, at an increased relative air humidity and in dry air. The method’s linearity was investigated in the ranges 0.40–1.40 µg mL^?1 for isomer I and 0.40–2.40 µg mL^?1 for isomer II of perindopril l-arginine. The UHPLC-DAD method met the precision and accuracy criteria for the determination of the isomers of perindopril l-arginine. The limits of detection and quantitation were 0.1503 and 0.4555 µg mL^?1 for isomer I and 0.0356 and 0.1078 µg mL^?1 for isomer II, respectively.     

Liquid chromatography tandem mass spectrometry method for the quantitative analysis of ceritinib in human plasma and its application to pharmacokinetic studies

Ceritinib is a highly selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK). Because it is an investigational compound, there is a need to develop a robust and reliable analytical method for its quantitative determination in human plasma. Here, we report the validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the rapid quantification of ceritinib in human plasma. The method consists of protein precipitation with acetonitrile, and salting-out assisted liquid-liquid extraction (SALLE) using a saturated solution of sodium chloride prior to analysis by LC-MS/MS with electrospray ionization (ESI) technique in positive mode. Samples were eluted at 0.800 mL min^?1 on Ascentis Express® C₁₈ column (50 mm?×?2.1 mm, 2.7 μm) with a mobile phase made of 0.1 % formic acid in water (A) and 0.1 % formic acid in acetonitrile (B). The method run time was 3.6 min and the low limit of quantification (LLOQ) was estimated at 1.00 ng mL^?1 when using 0.100 mL of human plasma. The assay was fully validated and the method exhibited sufficient specificity, accuracy, precision, and sensitivity. In addition, recovery data and matrix factor (MF) in normal and in hemolyzed plasmas were assessed, while incurred samples stability (ISS) for ceritinib was demonstrated for at least 21 months at a storage temperature of ?65 °C or below. The method was successfully applied to the measurement of ceritinib in clinical samples and the data obtained on incurred samples reanalysis (ISR) showed that our method was reliable and suitable to support the analysis of samples from the clinical studies.     

Online solid phase extraction LC–MS/MS method for the analysis of succinate dehydrogenase inhibitor fungicides and its applicability to surface water samples

A sensitive and selective analytical method, based on online solid phase extraction coupled to LC–MS/MS, was developed and validated to determine traces of several recently introduced fungicides in surface water and wastewater. The list of target analytes included eight succinate dehydrogenase inhibitors (bixafen, boscalid, fluopyram, flutolanil, fluxapyroxad, isopyrazam, penflufen, and penthiopyrad), and two other fungicides with different modes of action, fenpyrazamine and fluopicolide. Detection and quantification limits in various matrices were in the range of 0.1 to 2 and 0.5 to 10 ng/L, respectively. Moderate signal suppression was observed in surface water (≤15 %) and wastewater (≤25 %) and was well compensated by the selected internal standard. The intra- and inter-day precisions were generally <10 and <20 %, respectively. The applicability of the method was demonstrated in a study on the occurrence of fungicides in the river Glatt, Switzerland, that drains a catchment area of 419 km² with a substantial proportion of agricultural land. Of the studied compounds, only boscalid and fluopicolide were detected in flow-proportional weekly composite samples, generally at low concentrations up to 15 and 5 ng/L, respectively. While fluopicolide was detected in only 30 % of the samples above the LOD of 0.5 ng/L, boscalid was detected in all samples analyzed between March and October 2012. Graphical Abstract

Concentration of the fungicides boscalid and fluopicolide in flow-proportional weekly-composite watersamples from River Glatt, Switzerland in 2012     

An Approach to Transfer Methods from HPLC to UHPLC Techniques in Some Carbapenems

Stability-indicating LC methods were developed and validated for the quantitative determination of doripenem, meropenem and tebipenem in the presence of their degradation products formed during forced degradation studies. Isocratic HPLC and UHPLC separations were performed with a core–shell Kinetex 1.7, 2.6 and 5 µm, all C18, 100A, 100 × 2.1 mm columns and the mobile phase composed of acetonitrile and 12 mmol L^?1 ammonium acetate in different ratios. The flow rates of the mobile phase were: 0.5 mL min^?1 for 1.7 µm column, and 1.0 mL min^?1 for 2.6 and 5 µm ones. Detection wavelength was 298 nm and temperature was set at 30 °C. All analysed drugs were exposed to stress conditions which caused their hydrolysis and thermal degradation. The methods were validated by evaluation of linearity, accuracy, precision, selectivity and robustness. Proposed methods were successfully applied for the determination of investigated antibiotics during kinetic studies in aqueous solutions and in the solid state. The advantages of chromatographic procedures which are based on the use of C18 stationary phases with different particle sizes in the analysis of selected carbapenems were discussed.     

Solid phase inclusive immunoradiometric assay for human chorionic gonadotropin using monoclonal antibodies

Summary A simple, one step, inclusive immunoradiometric assay for human chorionic gonadotropin (hCG) employing monoclonal antibodies is described. Commercially available monoclonal antibodies from various commercial sources were screened. Identified “detection” antibody was radiolabeled with ¹²⁵I and the selected “capture” antibody was chemically coupled to magnetizable cellulose to form a solid phase. In the procedure developed, standard/sample, radiolabeled antibody and capture antibody were incubated together for 3 hours at room temperature with shaking. After incubation, the bound complex was quantitated for the associated radioactivity. The analytical sensitivity observed was 1.0 mIU/ml with a wide concentration range up to 1000 mIU/ml of hCG. “High dose hook” of the developed assay was observed beyond 2000 mIU/ml. Results showed that the developed assay had a good precision: intra-assay CV less than 8%, inter-assay CV less than 10% and good analytical recovery of 97-109%. The clinical samples analyzed by the developed procedure showed a good correlation with that of the commercial kit (r = 0.92; y = 0.99x+0.51).     

Preparation and characterization of cellulose nanocrystals via ultrasonication-assisted FeCl3-catalyzed hydrolysis

Cellulose nanocrystals (CNC) was obtained from bamboo pulp via ultrasonication-assisted FeCl₃-catalyzed hydrolysis process, with parameters optimized by response surface methodology. The optimal parameters were reaction temperature: 107 °C, reaction time: 58 min, ultrasonication time: 186 min. The morphological, crystal structural, chemical structural and thermal features of the prepared cellulose nanocrystals were analyzed by scanning electron microscopy, transmission electron microscopy, X-ray diffraction (XRD), Fourier transfer infrared (FTIR) and thermogravimetric analysis. The results showed that the cellulose nanocrystals formed an interconnected network structure and CNC was rod-like with the length of 100–200 nm and the width of 10–20 nm. XRD result revealed that, compared with cellulose pulp, the crystallinity index of CNC increased from 69.5 to 79.4 %, while the cellulose I crystal structure remained. FTIR analysis demonstrated that CNC had the similar chemical structures to that of cellulose pulp, which indicated that the chemical structures of CNC remained unchanged in the presence of FeCl₃-catalyzed hydrolysis process and ultrasonication treatment. Thermogravimetric analysis revealed that the resulting CNC exhibited relatively high thermal stability. The research shows that ultrasonication-assisted FeCl₃-catalyzed hydrolysis could be a highly efficient method for preparing CNC.     

A polyaniline-magnetite nanocomposite as an anion exchange sorbent for solid-phase extraction of chromium(VI) ions

This work describes a novel polyaniline-magnetite nanocomposite and its application to the preconcentration of Cr(VI) anions. The material was obtained by oxidative polymerization of aniline in the presence of magnetite nanoparticles. The parameters affecting preconcentration were optimized by a Box-Behnken design through response surface methodology. Extraction time, amount of magnetic sorbent and pH value were selected as the main factors affecting sorption. The sorption capacity of the sorbent for Cr(VI) is 54 mg g^?1. The type, volume and concentration of the eluents, and the elution time were selected as main factors in the optimization study of the elution step. Following sorption and elution, the Cr(VI) ions were reacted with diphenylcarbazide, and the resulting dye was quantified by HPLC with optical detection at 546 nm. The limit of detection is 0.1 μg L^?1, and all the relative standard deviations are <6.3 %. The nanocomposite was successfully applied to the rapid extraction and determination of trace quantities of Cr(VI) ions in spiked water samples. Figure

A schematic procedure of magnetic solid phase extraction     

Assay of Diastereoisomers of Cefuroxime Axetil in Amorphous and Crystalline Forms Using UHPLC-DAD

A sensitive UHPLC-DAD method was developed for determination of diastereoisomers of cefuroxime axetil in bulk substance in amorphous and crystalline forms as well as in pharmaceutical preparations. Chromatographic separation was achieved on Kinetex C-18 (100 mm × 2.1 mm, 1.7 µm) column with mobile phase consisting of 0.1 % formic acid:methanol (88:12, v/v), at the flow rate of 0.7 mL min^?1 and total run time of 3 min. The wavelength of the DAD detector was set at 278 nm. Inter-day precision (RSD) was less than 3 % and accuracy level ranged between 98.31 and 104.99 %. Degradation products of cefuroxime axetil in aqueous solutions and in the solid state were identified with a EIS-Q-MS mass spectrometer. The solubility of above-mentioned polymorphic forms of cefuroxime axetil in suitable solvents is a crucial factor during preparation of samples and is essential for chromatographic separation of its diastereoisomers.     

Antimicrobial activity of silver nanoparticles in situ growth on TEMPO-mediated oxidized bacterial cellulose

In order to improve the antimicrobial activity of bacterial cellulose (BC), the silver nanoparticles (Ag NPs) were in situ fabricated on the BC membranes, affording BC and Ag hybrid antimicrobial materials, BC + Ag, which possesses excellent antimicrobial performance. Typically, carboxyl groups were firstly introduced into BC by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation. Then, the carboxyl-functionalized BC was performed with ion-exchange reaction to change the sodium ions into Ag⁺ by immersing in AgNO₃ aqueous solution, generating Ag⁺ anchored BC. Finally, two types of distinct reductive reagents including NaBH₄ and sodium citrate were employed to transform Ag⁺ into Ag NPs to fabricate BC + Ag. The diameters of Ag NPs were determined to be 3.8 nm for NaBH₄-reduced BC + Ag, and 22.0 nm for sodium citrate-reduced one, respectively. The silver content of BC + Ag were determined to be 1.944 and 2.895 wt% for NaBH₄-reduced sample and sodium citrate-reduced one, respectively. Two types of BC + Ag both showed a slow and persistent Ag⁺ release profile, but the NaBH₄-reduced one released much more Ag⁺ than that of sodium citrate under the same measurement condition. In-depth antibacterial analysis via the disc diffusion and colony forming count method disclosed that BC + Ag exhibited strong bactericidal effects against both Escherichia coli and Staphylococcus aureus. And the antibacterial activity of NaBH₄-reduced BC + Ag was higher than the sodium citrate-reduced one. Overall, this study would further improve the antibacterial efficiency of BC + Ag.     

A paper-based lateral flow assay for morphine

Morphine was used as a model analyte to examine the possibility of using cellulose, physically modified by papermaking and converting techniques, as a capillary matrix in a lateral flow type of diagnostic assay. This research was directed toward low-cost, disposable, and portable paper-based diagnostics, with the aim of addressing the analytical performance of paper as a substrate in the analysis for drugs of abuse. Antibody Fab fragments were used as sensing molecules, and gold nanoparticle detection was employed. Inkjet printing was used to pattern sensing biomolecules as detection zones on paper. To validate the usefulness of paper as a diagnostic platform, the principle of a direct sandwich assay, based on immunocomplex formation between morphine and the anti-morphine Fab fragment and detection of the formed immunocomplex by another Fab fragment, was implemented. Results were compared with that achieved by using nitrocellulose as a reference material. Possible interfering from the sample matrix on assay quality was investigated with spiked oral fluid samples. Under optimized conditions, a visually assessed limit of detection for the sandwich assay was 1 ng/mL, indicating that the paper-based test devices developed in this work can perform screening for drugs of abuse and can fulfill the requirement for a sensitive assay in diagnostically relevant ranges. Fig

?     

Preconcentration of ultra-trace amounts of iron and antimony using ion pair solid phase extraction with modified multi-walled carbon nanotubes

Ion pair solid phase extraction was applied to the simultaneous preconcentration of iron and antimony. The ion pairs consisting of FeCl₄ ^? or SbCl₄ ^? anions and the benzyldimethyltetradecyl ammonium cation were formed on the surface of multi-walled carbon nanotubes, then eluted with nitric acid, and the elements finally quantified by ETAAS. The adsorption capacities of the impregnated MWCNTs are 9.2 mg g^?1 for iron and 27.5 mg g^?1 for antimony. The following analytical figures of merit were determined for iron and antimony, respectively: Enrichment factors of 210 and 230, assay precisions of ±5.3 % and ±4.8 %, linear calibration plots from 0.7 to 9.4 and 13.0 to 190 ng L^?1, and detection limits of 0.17 and 3.5 ng L^?1. The method was applied to the determination of iron and antimony in human hair, synthetic sample, and to the certified reference materials gold ore (MA-1b) and trace elements in water (SRM 1643d).

Laser diode thermal desorption atmospheric pressure chemical ionization tandem mass spectrometry applied for the ultra-fast quantitative analysis of BKM120 in human plasma

A sensitive and ultra-fast method utilizing the laser diode thermal desorption ion source using atmospheric pressure chemical ionization coupled to tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for the quantitative analysis of BKM120, an investigational anticancer drug in human plasma. Samples originating from protein precipitation (PP) followed by salting-out assisted liquid-liquid extraction (SALLE) were spotted onto the LazWell? plate prior to their thermal desorption and detection by tandem mass spectrometry in positive mode. The validated method described in this paper presents a high absolute extraction recovery (>90 %) for BKM120 and its internal standard (ISTD) [D₈]BKM120, with precision and accuracy meeting the acceptance criteria. Standard curves were linear over the range of 5.00 to 2000 ng mL^?1 with a coefficient of determination (R ²) >0.995. The method specificity was demonstrated in six different batches of human plasma. Intra- and inter-run precision as well as accuracy within ±20 % at the lower limit of quantification (LLOQ) and ±15 % (other levels) were achieved during a three-run validation for quality control (QC) samples. The post-preparative stability on the LazWell? plate at room temperature was 72 h and a 200-fold dilution of spiked samples was demonstrated. The method was applied successfully to three clinical studies (n?=?847) and cross-checked with the validated LC-ESI-MS/MS reference method. The sample analysis run time was 10 s as compared to 4.5 min for the current validated LC-ESI-MS/MS method. The resultant data were in agreement with the results obtained using the validated reference LC-ESI-MS/MS assay and the same pharmacokinetic (PK) parameters were calculated for both analytical assays. This work demonstrates that LDTD-APCI-MS/MS is a reliable method for the ultra-fast quantitative analysis of BKM120 which can be used to speed-up and support its bioanalysis in the frame of the clinical trials.     

Nano-gold capillary immunochromatographic assay for parvalbumin

A novel non-instrumental bioanalysis based on colloidal-gold immunochromatography in a modified glass capillary was developed and named capillary immunochromatographic assay (CICA). In this report, glass capillary was proposed as a support in immunochromatographic assay because of its excellent characteristics. Goat anti-rabbit IgG and parvalbumin (PV) were immobilized on the inner wall of the glass capillary as control zone and test zone, respectively. The CICA was constructed, and main variables for the performance were optimized. Using an important allergen of fish products (parvalbumin, PV) as the target, the analytical efficiency of the developed technique was investigated and the visual detection limit (VDL) and semi-quantitative limit of detection (LOD) were estimated to be 70 ng mL^?1 and 40 ng mL^?1, respectively. The coefficient of variation (CV) for the intra-assay and inter-assay was calculated for the PV concentration of 50 ng mL^?1, and the entire operation, including sample preparation, was consistently performed in 30 min. The developed technique was implemented and validated with different foodstuffs, including Scophthalmus maximus (Linnaeus), surimi products, and livestock, confirming sufficient accuracy and precision of results and verifying the method to be efficacious. These results enabled us to propose CICA as a new and promising technique for simple, rapid, and on-site screening of PV in biological samples. Graphical abstract

The scheme of the CICA system: (a) the control zone and test zone on the capillary, (b) negative results and (c) positive results     

Radiolanthanide-labeled HA particles in the treatment of rheumatoid arthritis: ready-to-use cold kits for rapid formulation in hospital radiopharmacy

Hydroxyapatite (HA) [Ca₁₀(PO₄)₆(OH)₂] particles radiolabeled with a variety of β^? emitting lanthanide radionuclides and also pseudolanthanide ⁹⁰Y have been proposed for the treatment of arthritis. A ready-to-use cold kit of HA particles (1–10 µm size) was developed for fast and convenient formulation of radiolanthanide-labeled HA particles at hospital radiopharmacy. Six radionuclides namely, ¹⁶⁹Er, ¹⁷⁷Lu, ¹⁵³Sm, ¹⁶⁶Ho, ¹⁴²Pr and ⁹⁰Y, having β^? emissions of a wide range of energy [E_β(max) = 0.34–2.28 MeV] were identified and produced by thermal neutron activation. Clinical doses of HA particles labeled with these radionuclides were prepared in high yield (>97 %) and radiochemical purity (>99 %) using the cold kits. Pre-clinical studies of ¹⁷⁷Lu–HA carried out in Wistar rats bearing arthritis in knee joints revealed no leakage of the activity from the joints. In preliminary clinical investigation using 333 ± 46 MBq doses of the same preparation, significant improvement in the disease conditions was reported in patients with chronic rheumatoid arthritis of knee joints.