Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum

Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10–1000 ng/mL), with adequate accuracy (90.1–114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.     

A polar macroporous sorbent for gas chromatography

Summary The gas chromatographic behaviour of crosslinked macroporous 2-hydroxyethyl methacrylate grafted with 2-methyloxazoline was investigated and the range of applicability of the copolymer was assessed. Retention index values were measured on this copolymer and compared with those obtained on the terpolymer 2-hydroxyethyl methacrylate-ethylene dimethacrylate-acrylonitrile. Rohrschneider constants and efficiency data for selected sorbates are given. The use of this type of polymer in the separation of various types of compounds is documented by various examples.     

Yttrium aluminate crystals for slabs

The methods of growing YAG:Nd crystals with a flat interface and YAP:Nd crystals with a sharp conical interface are described. The form of the interface was controlled by the He and H₂O content in the reducing atmosphere composed mainly of Ar and H₂ as well as by axial temperature gradient above the melt level. The crystals of 120–180 mm in length were machined to the high-quality slabs.     

Determination of 8-hydroxy-2'-deoxyguanosine in untreated urine by capillary electrophoresis with UV detection

A capillary electrophoresis method with UV detection was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in untreated urine samples. The calibration graph for 8-OHdG in urine is linear in the concentration range 10-500 mg/l. and the detection limit is 5 mg/l (17 microM). 8-OHdG was determined in urine from oncological patients treated by radiation therapy. Its concentrations relative to creatinine were found to be in the range 10-47 microg 8-OHdG/l mg creatinine (4-19 micromol 8-OHdG/mmol creatinine). The overall time of the analysis of a urine sample was less than 15 min.     

Validated HPLC–MS–MS method for determination of azithromycin in human plasma

A validated, highly sensitive, and selective HPLC method with MS–MS detection has been developed for quantitative determination of azithromycin (AZI) in human Na₂EDTA plasma. Roxithromycin (ROX) was used as internal standard. Human plasma containing AZI and internal standard was ultrafiltered through Centrifree Micropartition devices and the concentration of AZI was determined by isocratic HPLC–MS–MS. Multiple reaction monitoring mode (MRM) was used for MS–MS detection. The calibration plot was linear in the concentration range 2.55–551.43 ng mL⁻¹. Inter-day and Intra-day precision and accuracy of the proposed method were characterized by R.S.D and percentage deviation, respectively; both were less than 8%. Limit of quantification was 2.55 ng mL⁻¹. The proposed method was used to determine the pharmacokinetic profile of AZI (250-mg tablets).     

Influence of ion bombardment on growth and properties of PLD created DLC films

A hybrid PLD system with ion bombardment of films was developed. Growing DLC films were modified during the laser deposition (10 J?cm^?2) by argon ions with energy in the range from 40 eV to 210 eV and cathode current of 0.15 A and 0.5 A. The content of sp² “graphitic” and sp³ “diamond” bonds was measured using XPS. Sp³ bonds changed from 60 % to 81 %. We found the highest sp³ content for energy of 40 eV. Hardness (and reduced Young’s modulus) were determined by nanoindentation and reached 49 GPa (277 GPa). Film adhesion was studied using the scratch test and was up to 14 N for titanium substrates. Relations among deposition conditions and measured properties are presented.     

A Photochemical/Thermal Switch Based on 4,4′-Bis(benzimidazolio)stilbene: Synthesis and Supramolecular Properties.

Stilbene derivatives are well-recognised substructures of molecular switches based on photochemically and/or thermally induced (E)/(Z) isomerisation. We combined a stilbene motif with two benzimidazolium arms to prepare new sorts of supramolecular building blocks and examined their binding properties towards cucurbit[n]urils (n=7, 8) and cyclodextrins (β-CD, γ-CD) in water. Based on the ¹H NMR data and molecular dynamics simulations, we found that two distinct complexes with different stoichiometry, i. e., guest@β-CD and guest@β-CD₂, coexist in equilibrium in a water solution of the (Z)-stilbene-based guests. We also demonstrated that the bis(benzimidazolio)stilbene guests can be transformed from the (E) into the (Z) form via UV irradiation and back via thermal treatment in DMSO.     

Study of nanocrystalline diamond film growth in rf hybrid laser deposition systems in O2, H2 and H2+Ar ambients

Pulsed laser deposition (PLD) and hybrid pulsed laser deposition (HPLD) systems were used for nanocrystalline diamond (NCD) film growth on Si(100) and sapphire(0001) substrates. The PLD system was based on a KrF excimer laser (=248 nm,20 ns), which ablated a graphite target in pure oxygen or hydrogen ambient. The HPLD system was based on a combination of PLD and additional capacitively coupled radio-frequency discharges (13.56 MHz) in argon–hydrogen ambient. Radio-frequency power was applied to two plane parallel electrodes or directly to the substrate holder. The working atmosphere pressure was varied from 1 Pa to 220 Pa and the substrate temperature was varied from 20 °C to 660 °C. X-ray diffraction analysis, Raman spectroscopy and a profilometer were used to study the deposited film properties. A band around 1180 cm^-1, which can be attributed to NCD, occurred in the Raman spectra. A characteristic diamond peak at 1332 cm^-1 was not observed. Films prepared by HPLD showed better compositional homogeneity (from Raman analysis) than films created by PLD. PACS 52.80.Pi; 81.07.Bc; 81.15.Fg     

Cr:Tm:Ho:YAG (2.1 μm) and Nd:YAG (1.444 μm) pulsed-laser lithotripsy of bile duct stones

The Nd:YAG (1.444 m) and Cr:Tm:Ho:YAG (2.1 m) free-running laser systems of the output energy of 300 mJ per pulse and repetition rate 1 Hz have been developed and used for bile duct stones fragmentation study in vitro. A total of 67 human bile duct stones of known sizes, collected from surgical sources were used in the experiments. Insensitivity of the stones fragmentation to the type of the laser used, and insensitivity of the fragmentation efficiency to the type of stone, was observed. No pathological changes of the tissue were observed for non-human soft tissue laser irradiation (in vitro) by 1, 2, and 5 pulses of the Cr:Th:Ho:YAG radiation of the fluency of 1.6 J/cm². The lasers are found to be good candidates for laser lithotripsy.