Science Labormed Pharma SA and

Bucharest, Romania

Science Labormed Pharma SA and

Bucharest, Romania
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Udrescu S.,Science Labormed Pharma SA and | Sora I.D.,Science Labormed Pharma SA and | Albu F.,Science Labormed Pharma SA and | David V.,University of Bucharest | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

Large volume injection of samples in strong diluents immiscible with the mobile phases used in reversed phase liquid chromatography (RPLC) has been recently introduced in practice. In the present work, the potential of the technique has been evaluated for bioanalytical applications. The process consists of the liquid-liquid extraction of indapamide from whole blood into 1-octanol, followed by the direct injection from the organic layer into the LC. Detection was made through negative electrospray ionization (ESI) and tandem mass spectrometry (MS2). The method was developed, validated, and successfully applied to a large number of samples in two bioequivalence studies designed for indapamide 1.5mg sustained release and 2.5mg immediate release pharmaceutical formulations. The performance of the analytical method is discussed based on data resulting from the validation procedure and the completion of the bioequivalence studies. © 2010 Elsevier B.V.


Voicu V.,University of Bucharest | Voicu V.,Romanian Army Center For Medical Research And 37 Ca Rosetti Street | Sora I.,Science Labormed Pharma SA and | Sarbu C.,Babes - Bolyai University | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2010

Chromatographic retention data obtained from interactions between some oxime-type compounds and different stationary phases (involving hydrophobic interaction, ion pairing formation availability, π-π, H-bonding, dipole-dipole, ion-dipole, electrostatic interaction and glycoprotein binding ability) have been studied. The logarithms of the capacity factors extrapolated at 0% or 100% organic solvent, resulting from the functional dependencies between retention and mobile phase composition, were used for estimation of different kind of hydrophobicity or hydrophilicity descriptors (HHDs) of these compounds. The conditions of the chromatographic separation were chosen as close as possible to in-vivo conditions (the aqueous component of the mobile phase has a pH in the physiologic interval 6.8-7.2, 0.9% sodium chloride was added to reproduce ionic strength and isotonic character, and the temperature was set at 37°C). These descriptors characterizing the partition between stationary/mobile phases through specific interactions may be directly used for correlation to biological distribution processes, such as penetration of the blood/brain barrier. Oxime-type compounds used as acetylcholinesterase (AChE, E.C.3.1.1.7) reactivators have been considered for the retention study. The choice is supported by their use in the therapy of acute intoxication with organophosphorus AChE inhibitors (OPIs, especially nerve agents and pesticides), a rather complicated chemistry in solution and a relative lack of data about computational molecular descriptors used for modeling biological partition/distribution. Some correlations between the determined descriptors and computational values have also been discussed. © 2010 Elsevier B.V.


Tache F.,University of Bucharest | Udrescu S.,University of Bucharest | Udrescu S.,Science Labormed Pharma SA and | Albu F.,University of Bucharest | And 4 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

Substitution of acetonitrile (ACN) as organic modifier in mobile phases for liquid chromatography by mixtures of propylene carbonate (PC) and ethanol (EtOH) may be considered a greener approach for pharmaceutical applications. Such a replacement is achievable without any major compromise in terms of elution order, chromatographic retention, efficiency and peak symmetry. This has been equally demonstrated for reverse phase (RP), ion pair formation (IP) and hydrophilic interaction liquid chromatography (HILIC) separation modes. The impact on the sensitivity induced by the replacement between these organic solvents is discussed for UV-vis and mass spectrometric detection. A comparison between Van Deemter plots obtained under elution conditions based on ACN and PC/EtOH is presented. The alternative elution modes were also compared in terms of thermodynamic parameters, such as standard enthalpy (ΔH0) and entropic contributions to the partition between the mobile and the stationary phases, for some model compounds. Van't Hoff plots demonstrated that differences between the thermodynamic parameters are minor when shifting from ACN/water to PC/EtOH/water elution on an octadecyl chemically modified silicagel stationary phase. As long as large volume injection (LVI) of diluents non-miscible with the mobile phase is a recently developed topic having a high potential of greening the sample preparation procedures through elimination of the solvent evaporation stage, this feature was also assessed in the case of ACN replacement by PC/EtOH. © 2012 Elsevier B.V.


Tache F.,University of Bucharest | Tache F.,Science Labormed Pharma SA and | Nascu-Briciu R.D.,Babes - Bolyai University | Sarbu C.,Babes - Bolyai University | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

The retention behavior of some flavonoids in reversed phase liquid chromatography (RPLC) was investigated using different chemistries of the modified silicagel based stationary phases. Highly end-capped octadecyl silicagel (ODS), polar embedded linker octadecyl silicagel (SB-18 Aqua), phenyl silicagel and pentafluorophenyl modified silicagel (PFP) were used as stationary phases. The mobile phase consisted in acetonitrile/acidified water mixtures, at different fractions of volume. The lipophilicity was estimated through different chromatographic descriptors, as it follows: logk w, mlogk, S, φ 0 and PC1/logk. The chromatographic behavior observed on the mentioned stationary phases was evaluated by means of various graphical profiles and correlation matrices. Additionally, new information about the characteristics of the stationary phases and their (dis)-similarities were provided through lipophilicity charts and by scatterplots of loadings obtained by applying principal component analysis (PCA) to retention data. Furthermore, the experimental lipophilicity indices estimated from retention data were correlated with the computed descriptors, at a high level of statistical significance. © 2011 Elsevier B.V.


Voicu V.,University of Bucharest | Gheorghe M.C.,University of Bucharest | Sora I.D.,Science Labormed Pharma SA and | Sarbu C.,Babes - Bolyai University | And 2 more authors.
Bioanalysis | Year: 2011

Background: The inherent reproducibility of a bioanalytical approach is usually sustained through incurred sample reanalysis (ISR). Questions relating to the number of ISRs, the right moment for performing reanalysis, the way of performing an appropriate statistical refinement of experimental data and actions to be taken in the case of failure are frequently raised. Results: Data resulting from ISR following a bioequivalence study for spironolactone formulations are discussed. Reanalysis of samples was carried out twice: immediately after the end of the study and after a period that overcame the long-term stability study achieved during method validation. The Bland-Altman approach was used to assess experimental results. ISR was successful over the short reanalysis period for both compounds. Data produced through reanalysis after the long-term period indicated a systematic positive bias for the metabolite canrenone (although results supported reproducibility). The results obtained for spironolactone were affected by a strong negative systematic bias and failed to support reproducibility. The explanation deals with the continuous conversion of spironolactone to canrenone in plasma samples. However, reproducibility of the method may be sustained by comparing original and repeated differences between concentration values in samples by means of a paired t-test, Wilcoxon sign rank-sum test and linear regression. Conclusions: Different statistical approaches for making data comparisons are discussed and may be successfully applied during reanalysis of samples from a bioequivalence study. Results of the evaluations may differ in accordance with the statistical procedure being applied, thus a definitive conclusion requires consideration of all specific experimental circumstances arising during production of the processed data. © 2011 Future Science Ltd.


Cheregi M.,University of Bucharest | Albu F.,University of Bucharest | Albu F.,Science Labormed Pharma SA and | Udrescu S.,University of Bucharest | And 4 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2013

Green bioanalytical approaches are oriented toward minimization or elimination of hazardous chemicals associated to bioanalytical applications. LC/MS-MS assay of enalapril and enalaprilat in human plasma was achieved by elimination of acetonitrile from both sample preparation and chromatographic separation stages. Protein precipitation (PP) by acetonitrile addition was replaced by liquid-liquid extraction (LLE) in 1-octanol followed by direct large volume injection of the organic layer in the chromatographic column operated under reversed phase (RP) separation mechanism. At the mean time, acetonitrile used as organic modifier in the mobile phase was successfully replaced by a mixture of propylene carbonate/ethanol (7/3, v/v). Three analytical alternatives ((I) acetonitrile PP. +. acetonitrile based chromatographic elution; (II) 1-octanol LLE. +. acetonitrile based chromatographic elution; (III) 1-octanol LLE. +. propylene carbonate/ethanol based chromatographic elution) were validated and the quality characteristics were compared. Comparison between these alternative analytical approaches was also based on results obtained on incurred samples taken during a bioequivalence study, through application of the Bland-Altman procedure. © 2012 Elsevier B.V.


Grinberg N.,Boehringer Ingelheim Pharmaceuticals | Albu F.,Science Labormed Pharma SA and | Fandrick K.,Boehringer Ingelheim Pharmaceuticals | Iorgulescu E.,University of Bucharest | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

Dimethyl sulfate (DMS) is frequently used in pharmaceutical manufacturing processes as an alkylating agent. Trace levels of DMS in drug substances should be carefully monitored since the compound can become an impurity which is genotoxic in nature. Derivatization of DMS with dibenzazepine leads to formation of the N-methyl derivative, which can be retained on a reversed phase column and subsequently separated from other potential impurities. Such derivatization occurs relatively slowly. However, it can be substantially speed up if ionic liquids are used as reaction media. In this paper we report the use of 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (IL1) and 1-butyl-4-methylpyridinium tetrafluoroborate (IL2) as reaction media for the derivatization of DMS with dibenzazepine. It was determined that the stoichiometry between the substrate and DMS may be 1:1 or 2:1, in relation with the nature of the reaction media. An (+)ESI-MS/MS approach was used for quantitation of the derivatized product. Alternatively, DMS derivatization may be carried out with pyridine in acetonitrile (ACN). The N-methylpyridinium derivative was separated by hydrophilic interaction liquid chromatography (HILIC) and detected through (+)ESI-MS (in the SIM mode). In both cases, a limit of quantitation (LOQ) of 0.05 μg/ml DMS was achievable, with a linearity range up to 10 μg/ml. Both analytical alternatives were applied to assay DMS in 4-(2-methoxyethyl)phenol, which is used as a starting material in the synthesis of metoprolol. © 2012 Elsevier B.V.


PubMed | Science Labormed Pharma SA and
Type: Journal Article | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2011

Large volume injection of samples in strong diluents immiscible with the mobile phases used in reversed phase liquid chromatography (RPLC) has been recently introduced in practice. In the present work, the potential of the technique has been evaluated for bioanalytical applications. The process consists of the liquid-liquid extraction of indapamide from whole blood into 1-octanol, followed by the direct injection from the organic layer into the LC. Detection was made through negative electrospray ionization (ESI) and tandem mass spectrometry (MS(2)). The method was developed, validated, and successfully applied to a large number of samples in two bioequivalence studies designed for indapamide 1.5mg sustained release and 2.5mg immediate release pharmaceutical formulations. The performance of the analytical method is discussed based on data resulting from the validation procedure and the completion of the bioequivalence studies.

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