AQbD-Oriented UHPLC/MS/MS Method Development for Glycopeptides Assessment in Pharmaceutical Forms.

Vancomycin and teicoplanin are glycopeptide antibacterials that inhibit the bacteria cell wall synthesis showing activity against gram-positive bacteria. Development of the sensitive method is of great importance for quality control of these drugs that are fermentation products. Modification of the fermentation conditions could cause the differences in the relative amount of the total substance or component, as it is the case with teicoplanin.

Desquamative interstitial pneumonia with clinical, radiological and histologic correlation.

Respiratory bronchiolitis-associated interstitial lung disease (ILD), desquamative interstitial pneumonia (DIP), and pulmonary Langerhans cell histiocytosis are entities of smoking-related ILD. While clinically regarded as 2 separate forms of idiopathic interstitial pneumonia, DIP, and respiratory bronchiolitis-associated ILD are thought to be representing ends of a continuous spectrum of disease that primarily affects tobacco smokers. This case report presents a 53-year-old female patient who has 58 pack-year smoking history who has been experiencing a dry cough and epigastric pains for 2 years.

Analytical Quality by Design-based development and validation of ultra pressure liquid chromatography/MS/MS method for glycopeptide antibiotics determination in human plasma.

Aim: An ultra pressure liquid chromatography (UPLC)/MS/MS method for vancomycin and teicoplanin determination in human plasma was developed in accordance with analytical quality by design (AQbD) concept and fully validated.

Materials & Methods: Chromatographic separation was performed on ACQUITY UPLC C charge surface hybrid (CSH) column (2.1 mm × 50 mm, 1.

Factors associated with patient and health system delays in diagnosis and treatment of tuberculosis in Montenegro, 2015-2016.

Background: Fundamental measures of control of tuberculosis are early detection and timely treatment of the affected. The aim of this study was to identify factors associated with patient-related and health system-related delays among patients with tuberculosis in the Republic of Montenegro.

Methods: A cross-sectional study included 130 tuberculosis patients older than 15 years of age.

Determination of olopatadine in human tears by hydrophilic interaction liquid chromatography-MS/MS method.

Aim: The objective of the study was development of hydrophilic interaction liquid chromatography-ESI/MS/MS method for the determination of olopatadine in tear matrix.

Materials & Methods: Separation was performed on Acquity BEH amide column (2.1 × 100 mm, 1.

Quality by Design in the development of hydrophilic interaction liquid chromatography method with gradient elution for the analysis of olanzapine.

This paper deals with the development of hydrophilic interaction liquid chromatography (HILIC) method with gradient elution, in accordance with Analytical Quality by Design (AQbD) methodology, for the first time. The method is developed for olanzapine and its seven related substances. Following step by step AQbD methodology, firstly as critical process parameters (CPPs) temperature, starting content of aqueous phase and duration of linear gradient are recognized, and as critical quality attributes (CQAs) separation criterion S of critical pairs of substances are investigated.

Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines.

In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior.

Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology.

In this paper, the development of reversed-phase liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality by design (QbD) approach is presented. The defined analytical target profile (ATP) was the efficient baseline separation and the accurate determination of the investigated analytes. The selected critical quality attributes (CQAs) were the separation criterions between the critical peak pairs because the mixture complexity imposed a gradient elution mode.

Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods.

In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte.

The influence of salt chaotropicity, column hydrophobicity and analytes' molecular properties on the retention of pramipexole and its impurities.

The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of different hydrophobicity (C8 and C18 XTerra(®) columns), as well as their common influence on the retention behavior of pramipexole and its structurally related impurities. The extended thermodynamic approach enabled the understanding of the underlying separation mechanism. Comparing six different column-salt systems it was observed that general system hydrophobicity presented by salt chaotropicity and column hydrophobicity favors stationary phase ion-pairing over the ion-pair formation in the eluent.

Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles.

The aim of this paper is to present a development of liquid chromatographic method when chaotropic salts are used as mobile phase additives following the QbD principles. The effect of critical process parameters (column chemistry, salt nature and concentration, acetonitrile content and column temperature) on the critical quality attributes (retention of the first and last eluting peak and separation of the critical peak pairs) was studied applying the design of experiments-design space methodology (DoE-DS). D-optimal design is chosen in order to simultaneously examine both categorical and numerical factors in minimal number of experiments.

Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and application to clinical practice.

This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time.

[Diffuse alveolar hemorrhage in isolated pulmonary capillaritis--case report].

Introduction: Pulmonary capillaritis is a small-diameter vessel vasculitis of the lung, which may occur in isolation as in isolated pauci-immune capillaritis, usually associated with the systemic vasculitis but it could be also related to collagen vascular diseases and in lung transplant rejection. Pulmonary capillaritis leads to diffuse alveolar hemorrhage.The clinical presentation includes symptoms like dyspnea, cough, pleuritic chest pain, fever and hemoptysis.

Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography.

In this paper, the capability of a polynomial-modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three-step procedure based on indirect modeling of peak width at 10% of peak height (W0.1), individual values of left-half width (A) and right-half width (B), number of theoretical plates (N), and tailing factor (Tf).

Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography.

Hydrophilic interaction liquid chromatography (HILIC) has emerged in recent years as a valuable alternative to reversed-phase liquid chromatography in the analysis of polar compounds. Research in HILIC is divided into two directions: the assessment of the retention mechanism and retention behavior, and the development of HILIC methods. In this work, four polar neutral analytes (iohexol and its related compounds A, B, and C) were analyzed on two silica and two diol columns in HILIC mode with the aim to investigate thoroughly the retention mechanisms and retention behavior of polar neutral compounds on these four columns.

The influence of inorganic salts with chaotropic properties on the chromatographic behavior of ropinirole and its two impurities.

Chaotropic agents recently gained popularity as interesting and useful mobile phase additives in liquid chromatography due to their effect on analytes retention, peak symmetry and separation efficiency. They mimic the role of classical ion-pairing agents, but with less drawbacks, so their use becomes attractive in the field of pharmaceutical analysis. In this paper, the influence of sodium trifluoroacetate and sodium perchlorate on the chromatographic behavior of ropinirole and its impurities is examined.

Changing trends in incidence of lung cancer by histological type in Montenegro.

Introduction: Lung cancer is one of the most common malignant neoplasms, as well as the most common cause of death cancer. Most lung cancers are squamous cell carcinomas, small cell carcinomas or adenocarcinomas.

Objective: Examining changes in trends of lung cancer incidence in Montenegro by histological type during a 15-year period, from 1997 to 2011.

Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative.

Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design.

In this article, a step-by-step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate-mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal-to-noise ratios, to be improved, enabling achievement of lower limit of detection values.

Improved chromatographic response function in HILIC analysis: application to mixture of antidepressants.

This paper presents exploration of chromatographic behavior in HILIC system by experimental design and improved chromatographic response function denoted as N(CRF)*. As a model mixture six antidepressants were chosen: selegiline, mianserine, sertraline, moclobemide, fluoxetine and maprotiline. Due to complexity of retention mechanisms in HILIC system, detailed examination of experimental space assessing the influence of important factors (acetonitrile content in the mobile phase, buffer concentration and pH of the mobile phase) and their interactions was done by applying 3(3) experimental design.

Assessment of β-lactams retention in hydrophilic interaction chromatography applying Box-Behnken design.

In this paper, the retention prediction models for mixture of β-lactam antibiotics analyzed by hydrophilic interaction chromatography (HILIC) are presented. The aim of the study was to investigate the retention behavior of some organic acids and amphoteric compounds including cephalosporins (cefotaxime, cefalexin, cefaclor, cefuroxime, and cefuroxime axetil) and penicillins (ampicillin and amoxicillin). Retention of substances with acidic functional group in HILIC is considered to be interesting since the majority of publications in literature are related to basic compounds.

Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder.

Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross-linking cornified cell envelope proteins.

Advancement in optimization tactic achieved by newly developed chromatographic response function: application to LC separation of raloxifene and its impurities.

In this paper a new chromatographic response function (CRF) is designed and proposed for utilization in the optimization strategies. The function capability to represent the overall quality of a experimentally obtained chromatograms was compared to the other two objective functions and proved to give more accurate and reliable results. The new CRF has improved concept of separation and time term estimation.

Validation of an oil-in-water microemulsion liquid chromatography method for analysis of perindopril tert-butylamine and its impurities.

This paper describes the development and validation of a microemulsion liquid chromatography (MELC) method for simultaneous determination of perindopril tert-butylamine and its impurities in bulk active substances and the pharmaceutical dosage form of tablets. An appropriate resolution with reasonable retention times was obtained for a microemulsion containing 0.24% (w/v) butyl acetate, 0.

Validation of a column liquid chromatographic method for the analysis of pramipexole and its five impurities.

In this paper, a previously optimized method for HPLC analysis of pramipexole and its impurities was subjected to method validation in accordance with official regulations. The optimized chromatographic conditions were as follows: mobile phase acetonitrile-water phase [15 + 85, v/v, water phase contained 1% triethylamine (TEA), pH adjusted to 7.0 with orthophosphoric acid]; detection at 262 nm for pramipexole, BI-II 751 xx, BI-I 786 BS, BI-II 820 BS, and 2-aminobenzothiazole and at 326 nm for BI-II 546 CL; column temperature, 25 degrees C; and flow rate, 1 ml/min.