Decoding Rocks: An Assessment of Geomaterial Microstructure Using X-ray Microtomography, Image Analysis and Multivariate Statistics.

An understanding of the microstructure of geomaterials such as rocks is fundamental in the evaluation of their functional properties, as well as the decryption of their geological history. We present a semi-automated statistical protocol for a complex 3D characterization of the microstructure of granular materials, including the clustering of grains and a description of their chemical composition, size, shape, and spatial properties with 44 unique parameters. The approach consists of an X-ray microtomographic image processing procedure, followed by measurements using image analysis and statistical multivariate analysis of its results utilizing freeware and widely available software. The statistical approach proposed was tested out on a sandstone sample with hidden and localized deformational microstructures. The grains were clustered into distinctive groups covering different compositional and geometrical features of the sample's granular framework. The grains are pervasively and evenly distributed within the analysed sample. The spatial arrangement of grains in particular clusters is well organized and shows a directional trend referring to both microstructures. The methodological approach can be applied to any other rock type and enables the tracking of microstructural trends in grains arrangement.

Application of liquid chromatography method with electrochemical detection for bioequivalence study of trimetazidine in human plasma.

A method to estimate trimetazidine (CAS: 13171-25-0) levels in human plasma by means of HPLC with electrochemical detection was developed. Trimethoprim (CAS: 26807-65-8) was used as an internal standard. This method of analysis was fully validated according to the guidelines of the United States Food and Drug Administration, European Medicines Agency and Organization for Economic Co-operation and Development and Good Laboratory Practice rules. The accuracy and precision of the developed method were found to be satisfactory and stability studies showed acceptable variation (below 15%) of trimetazidine concentrations when samples were stored frozen at -75 degrees C for 54 days. The developed method was successfully used for a comparative 2 x 2 period, crossover bioequivalence study of two extended-release preparations of trimetazidine performed on 24 healthy volunteers at the steady state after multiple dosing of 35 mg twice daily for 4 days and a single 35 mg dose on the 5th day and after a single dose of 35 mg under fasting or postprandial conditions.

Application of ultra-performance columns in high-performance liquid chromatography for determination of albendazole and its metabolites in turkeys.

Methods for determination of albendazole (ALB), albendazole sulfoxide (SOX) and albendazole sulfone (SON) in turkey blood plasma, using high-performance liquid chromatography (HPLC) with fluorescence detection, were developed. Moreover, comparison of HPLC columns with ultra-performance liquid chromatography (UPLC) columns was performed. Albendazol was administered orally in 5-week-old birds (n = 18) at a dose of 25 mg/kg b.w. Accuracy and precision of the developed method were satisfactory and stability studies showed acceptable variation (below 15%) in ALB, SOX and SON concentrations when the samples were stored at -75°C for 15 days. UPLC(®) columns gave higher peaks from typical HPLC columns retaining high quality of analysis. Pharmacokinetic analysis indicated quick elimination of ALB from turkey blood plasma. The mean residence time of SON was at least two times longer than that of SOX and four times longer than that of ALB. The elimination half-lives for ALB, SOX and SON were 0.7 ± 0.27, 5.37 ± 6.03, 9.17 ± 5.12 h, respectively. The obtained results indicate that the described method allows for precise determination of albendazole and its metabolites in turkey plasma. Moreover, using UPLC columns in HPLC apparatus results in higher sensitivity as compared with the classical HPLC columns.

Chromatographic/mass spectrometric method for the estimation of itraconazole and its metabolite in human plasma. Application to a bioequivalence study.

A HPLC/mass spectrometry method for the estimation of itraconazole (CAS 84625-61-6, ITR) and its active metabolite hydroxyitraconazole (CAS 112559-91-8, HOX) in human plasma was developed. Terconazole (CAS 67915-31-5) was used as an internal standard. The analytical method was fully validated according to FDA and EMEA requirements. The accuracy and precision of the developed method was satisfactory and stability studies showed an acceptable variation (below 15%) of ITR and HOX concentrations when the samples were stored frozen at -75 degrees C for 95 days. The developed method was successfully used for a comparative 2 x 2 period, crossover bioequivalence study of two preparations of ITR (Itrakonazol Genexo 100 mg as the test drug) performed on 36 healthy volunteers.

Pharmacokinetic-pharmacodynamic relationship of rocuronium under stable nitrous oxide-fentanyl or nitrous oxide-sevoflurane anesthesia in children.

BACKGROUND: The aim of this study was to compare pharmacokinetics and pharmacokinetic-pharmacodynamic (PK-PD) relationship of rocuronium in children anesthetized with nitrous oxide (N2O) and fentanyl or with N2O and sevoflurane. METHODS: Twenty-four children (3-11 years old, ASA PS I or II) were randomized to receive N2O/O2-fentanyl or N2O/O2-sevoflurane (one MAC) anesthesia. Neuromuscular transmission was monitored electromyographically. Initial bolus dose of rocuronium, 0.6 mg x kg(-1) was followed by continuous infusion, targeting at steady-state 95% T1 depression. Neuromuscular transmission was allowed to recover spontaneously. Plasma samples were collected at the moment of discontinuation of infusion, and 10, 20, 30, 50, 60 and 75 min afterwards. Concentrations of rocuronium were measured using high-performance liquid chromatography with electrochemical detection (HPLC-EC). Rocuronium PK was described by a two-compartment model and PD parameters were estimated using effect compartment and sigmoidal E(max) models. RESULTS: No differences in rocuronium PK parameters were observed between study groups. Clearance was 3.91 +/- 2.07 and 3.62 +/- 0.80 ml x min(-1) x kg(-1) in sevoflurane and fentanyl groups, respectively (P < 0.65). Effect compartment concentrations corresponding to 50% inhibition of T1 (EC50) were 1.41 +/- 0.45 and 2.32 +/- 1.00 microg x ml(-1) (P < 0.02), and rate constants for equilibration between plasma and effect compartment (k(e0)) values were 0.10 +/- 0.04 and 0.24 +/- 0.14 min(-1) (P < 0.009) in sevoflurane and fentanyl groups, respectively. CONCLUSIONS: Disposition of rocuronium was similar under stable N2O-fentanyl and N2O-sevoflurane anesthesia. Sevoflurane reduced rocuronium requirements as well as decreased EC50 relevant to inhibition of T1 and rocuronium transfer to effect compartment. Therefore, the potentiating effect of sevoflurane seems to be mainly of PD origin, probably due to an increased sensitivity of the neuromuscular junction.