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WHO reported that there were 356,955,803 confirmed cases of COVID-19 and 5,610,291 deaths worldwide as of January 26, 2022 [1]. Meanwhile in Indonesia as of January 26, 2022, there were 4,301,193 positive cases of COVID- 19 and 144,254 deaths had been determined by the Ministry of Health of the Republic of Indonesia and the North Sulawesi Provincial Health Office reported 34,786 positive cases and 1,046 deaths [2]. During the COVID-19 pandemic, based on case reports, there were COVID-19 patients whose blood glucose levels increased while undergoing treatment at the hospital, even though these patients had no history of Diabetes mellitus. The effect of COVID-19 on increasing blood sugar levels is still not fully understood. Currently, while COVID-19 is still spreading, there is a need for continuous improvement in knowledge about the effective management of blood sugar control during COVID-19 infection. The purpose of this study was to investigate the relationship between blood glucose levels and clinical outcomes of COVID-19 patients undergoing treatment at the hospital. This research is a retrospective analysis using medical record data of Covid-19 patients treated at Sentra Medika Minahasa Utara Hospital for the period of March 2021 to August 2021. The results showed a significant relationship between elevated blood sugar levels and poor clinical outcomes in COVID-19 patients.

Isolated carbonate platforms are abundant and widespread in Cenozoic strata and in the present-day oceans of Southeast Asia. The purposes of this article are (1) to describe the basic oceanographic setting of present-day Southeast Asia oceans; (2) to synthesize, compare, and contrast observations of the character of extant platforms in the context of fundamental oceanographic controls; and (3) to leverage these insights to develop a more complete understanding of older isolated platforms, especially the Miocene systems of Central Luconia. The data, presented to mimic an offshore-to-nearshore transect, illustrate Holocene platforms with a spectrum of sizes, depositional relief, facies abundances, and water depths. Although the first-order patterns of relief, size, and orientation are controlled by the geologic setting and Pleistocene history, the results demonstrate the influences of physical processes (waves, tides, currents), siliciclastic sediment, and chemical oceanography (nutrients, salinity, temperature) on the sedimentologic and geomorphic character of these platforms. Careful and critical application of these concepts to Central Luconia reservoirs in isolated carbonate platforms provides actualistic examples and process-response analogs. Although these perspectives offer understanding into controls on horizontal and vertical reservoir heterogeneities, they also emphasize that any one modern system can only be a partial analog for an ancient reservoir in an isolated carbonate platform.

Sodium intake is very important in the mechanism of increasing blood pressure [1]. The effect of sodium intake in increasing blood pressure is through an increase in plasma volume (body fluid) and blood pressure [2]. The research was conducted in the form of an analytic survey with a cross-sectional study design. The data were processed using the SPSS program. The population is all students of SMAN 1 Amurang, South Minahasa District, the sample is taken by total sampling. From 67 samples, the minimum sodium content was 137 mEq/L and the maximum sodium content was 164. The average Na content was 143.54 mEq/L. The average systolic blood pressure was 119.04 mmHg and the average diastolic blood pressure was 79.70 mmHg. Based on the results of the Spearman correlation test, the correlation coefficient value (R = 0.069) with a significance of 0.579 for the correlation between sodium levels and systolic pressure. These results indicate that there is no statistically significant relationship between Na levels and systolic blood pressure. For the other Spearman correlation test results, the correlation coefficient value (R=-0.089) with a significance of 0.473 for the correlation between sodium levels and diastolic pressure. These results also show that there is no statistically significant relationship between sodium levels and diastolic blood pressure. It can be concluded that there is no relationship between serum sodium levels and blood pressure in adolescents in Amurang, South Minahasa District.

Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex® C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h.

ispartof: JOURNAL OF FOOD PROCESSING AND PRESERVATION vol:46 issue:11 status: published

Thin layer chromatography–flame ionization detection (TLC–FID) is a versatile analytical technique that can be used for fast analysis of organic compounds. It has been implemented in past decades for the analysis of lipids and petrochemical products, but rarely in other fields. Despite the improvement in the latest Iatroscan model and the introduction of an automatic programmable sample spotter, this system is still struggling to gain acceptance in universities and major research laboratories. The reason behind this might be a lack of awareness on the potential application of this system to other fields of analytical chemistry. This review presents TLC–FID as a mature and reliable, state of the art technique that combines the separation power of TLC with FID as a universal detector, which can be applied to the analysis of a wide variety of organic compounds. Basic operational procedures and previous literature, including its potential for ultrafast analysis of commercial samples, are discussed in order to create awareness on the potentials of this piece of equipment to other fields.

Tetracyclines (TCs) are a family of broad-spectrum antibiotics. During the manufacturing process or storage, epimerization of tetracyclines could occur, leading to 4-epimers which are nearly inactive. From an analytical point of view, isomers are often difficult to distinguish. Previously, four pairs of TCs (oxytetracycline, tetracycline, doxycycline, chlortetracycline and their respective 4-epimers) were differentiated by mass spectrometry (MS) through protonated ions. However, they do not follow common rules and so it is still quite difficult to differentiate between them. In order to solve this, the four pairs were differentiated in the current study by collision induced dissociation (CID) spectra of the alkali adduct ions, including lithium, sodium and potassium. In the spectra of the sodium adducts, all studied tetracyclines showed a tendency to form [M+Na-NH

The Apulia Carbonate Platform (ACP) is one of the most extensive isolated carbonate domains of the Tethyan Ocean, which persisted for a long span of time (Triassic to Miocene). The Late Jurassic to Eocene evolution of the ACP margin was characterised by different growth dynamics including progradation, aggradation and retrogradation; and by fundamental changes in platform profile. These changes were associated with significant fluctuations through time of the rates of sediment deposition, bypass and erosion along the slope, resulting in great variety in terms of deep-water resedimented carbonate facies and associated stratal architecture. In the Gargano Promontory (Southern Italy), also known as the spur of the Italian boot, the outcrops offer an easy access to a little deformed, complete platform-to-basin transect along the ACP margin. The different evolutionary stages of the slope and base-of-slope domains are well-exposed and can be directly related to the morphological evolution of the platform margin as well as to fluctuations of neritic carbonate production in response to tectonic, eustatic or oceanographic controls. The carbonate rocks of the Gargano Promontory are relevant analogues of some important subsurface reservoirs and plays of the Periadriatic domain, especially in the Adriatic offshore and below the Southern Apennines thrust-belt. This field itinerary includes four excursions with key stops providing an overview of lithofacies, stratal architecture and depositional processes from inner platform to basin environments. The selected outcrops are windows on the in-situ and remobilised sedimentary products of different carbonate factories that colonised the ACP margin through time, i.e. stromatoporoids in the Upper Jurassic-basal Cretaceous, rudists in the Cretaceous and large benthic foraminifera and corals in the Eocene. The excursions are organised chronologically focusing on: (1) Upper Jurassic – basal Cretaceous slope to basin transition, (2) Lower Cretaceous inner platform succession, (3) mid-Upper Cretaceous slope/base-of-slope deposits; and (4) middle Eocene shallow-marine to deep-marine deposits.

The world-class Middle-Upper Devonian carbonate outcrops of the Lennard Shelf, Canning Basin, Western Australia, allow for examination of long-term reefal carbonate shelf-to-basin systems within a variety of settings and contexts, including hierarchical accommodation trends, global biological crises, greenhouse-to-transitional climatic changes and syn-depositional tectonics. This complex Devonian record contained within the Lennard Shelf outcrop belt has spurred, and will continue to promote, research that advances the broader understanding of carbonate systems, highlights of which include: 1) sequence development across a long-term backstepping-to-progradational platform evolution; 2) ecological, depositional and geochemical expressions related global biotic crises; 3) platform-to-basin facies distributions and stratal architecture related to an interplay of carbonate controls; and 4) the characterisation and prediction of early-formed fracture networks in a variety of settings. The relationships between fine-scale, shelf-to-basin carbonate heterogeneity and seismic-scale stratigraphic architectures demonstrated in these well-preserved exposures also allows for the development of predictive conceptual models of relevance to carbonate hydrocarbon reservoirs in the age-equivalent Canadian Alberta Basin and younger Carboniferous reservoirs of the Pricaspian Basin in Kazakhstan.

Some easily applicable analytical methods were explored to evaluate the quality of personal care products containing aloe leaf gel. Aloins should be absent in these products in view of their side effects. To check this, liquid chromatography (LC) was applied.The LC method used a C18 monolithic column combined with gradient elution and ultraviolet (UV) detection. The mobile phase consisted of a mixture of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). The method was validated with respect to specificity, linearity, precision and accuracy. Next, it was practically applied for the analysis of commercial samples. In addition, the pH and moisture content were determined.The LC results indicated that aloins were detected in 25% of the analysed commercial samples. Further, it turned out that 42% of the test samples were found to be in the basic pH range and 33% of them contained excessive moisture.Proper quality control and adequate labelling of aloe leaf gel-based cosmetics are mandatory to avoid side effects.Certaines méthodes analytiques facilement applicables ont été explorée pour évaluer la qualité des produits de soins personnels contenants du gel de feuille d'aloe. Les aloïnes doivent être absentes de ces produits en raison de leurs effets secondaires. Pour vérifier cela, la chromatographie liquide (CL) a été appliquée. MÉTHODES: La méthode CL a utilisé une colonne monolithique C18 combinée à une élution par gradient et une détection ultraviolette (UV). La phase mobile était constituée d'un mélange de 0,1 % d'acide formique dans l'eau (A) et de 0,1 % d'acide formique dans l'acétonitrile (B). La méthode a été validée en ce qui concerne la spécificité, la linéarité, la précision et l'exactitude. Ensuite, elle a été appliquée pour l'analyse d'échantillons commerciaux. De plus, le pH et la teneur en humidité ont été déterminés. RÉSULTATS: Les résultats CL ont indiqué que des aloïnes ont été détectées dans 25 % des échantillons commerciaux analysés. Il s'est avéré que 42 % des échantillons se trouvaient dans la plage de pH basique et que 33 % d'entre eux contenaient une humidité excessive.Un contrôle de qualité approprié et un étiquetage adéquat des cosmétiques à base de gel de feuille d'aloe sont obligatoires pour éviter des effets secondaires.

Ion-pair liquid chromatography with pulsed electrochemical detection (LC-PED) was established for the analysis of impurities in arbekacin (ABK) sulfate. APursuit pentafluorophenylpropyl (PFP) column was used as stationary phase. This novel method showed greater separation and sensitivity ability. In a representative ABK sample, 24 impurity peaks were detected in LC-PED, where of only 9 were monitored by a post-column derivatization method prescribed by the Japanese Pharmacopoeia (JP). For identification of the chemical structures of the impurities detected by LC-PED, LC-Mass Spectrometry (MS) was used. Two challenges had to be overcome in this work. The first was the transfer of the MS incompatible mobile phase to an MS compatibleone while maintaining the elution order of the peaks in the chromatograms. Previously reported approaches such as two-dimensional (2D)LC were hardly applicable in this case due to the lack of ultraviolet (UV) absorbing chromophores in ABK and its impurities. The sodium hydroxide solution was replaced by aqueous ammonia to adjust the pH of the mobile phase used in LC-PED. The other challenge encountered was the ion suppression effect caused by trifluoroacetic acid (TFA) and pentafluoroproponic acid (PFPA) in the mobile phase. Some strategies such as "TFA-fixed" and its modifications were tried, but they were inconvenient and severe contamination of the MS was observed. A cationself-regenerating suppressor (CSRS), which was originally designed for increasing analyte conductivityof ammonia and amines analysis in ion chromatography (IC), was coupled between the LC and Ion Trap-Time of Flight (IT-TOF)-MS and almost all TFA and PFPA in the mobile phase were removed. The limit of detection (LOD) of ABK in this integrated system improved significantly to 20 ng/mL. The chemical structures of the 28 impurities were elucidated and 15 impurities were reported for the first time.

Exocrine pancreatic insufficiency (EPI) can be comfortably diagnosed by a breath test using the mixed triglyceride 2-octanoyl (1

Headspace gas chromatography (HS-GC) has the potential to be used for water determination in pharmaceutical products. In this article, its use for the determination of water in solid samples is explored without the need of dissolution by means of the full evaporation technique (FET). This way, water is thermally removed from a small amount of sample which is directly weighed in the vial. This simplifies considerably the method since no diluent has to be searched and HS saturation is avoided. Blank corrections were performed to compensate for atmospheric moisture variation. Moreover, the performance of mass spectrometry (MS) and thermal conductivity detection (TCD) was compared. The method showed excellent figures of merit when working with TCD, such as R2> 0.99 and RSD

ispartof: JOURNAL OF MASS SPECTROMETRY vol:54 issue:12 pages:1013-1018 ispartof: location:England status: published

Topical formulations are medications applied locally on the skin to treat ailment. They are made up of complex mixtures of active ingredients and excipients. Till date, no analytical method has been found in literature that is able to simultaneously analyze volatile and semi-volatile actives present in topical formulations. In this work, an analytical procedure by gas chromatography equipped with a programmed temperature vaporizing (PTV) inlet and a flame ionization detector was developed and validated for the simultaneous quantitative determination of volatile and semi-volatile actives such as camphor, L-menthol, methyl salicylate, ethyl salicylate, salicylic acid, glycol monosalicylate and capsaicin in a topical formulation. Liquid-liquid extraction was used to isolate the components of interest prior to injection into the gas chromatographic system. All target analytes were completely separated from each other and a linear calibration curve was achieved for all analytes with a determination coefficient > 0.995. 2-phenoxyethanol was used as internal standard for quantitation. Good repeatability and recovery values were achieved and reported. This method reports for the first time, the simultaneous quantitative analysis of volatile and semi-volatile active pharmaceutical ingredients in a single measurement. The developed method was successfully applied to the analysis of real pharmaceutical samples and the described analytical protocols can be recommended for routine analysis of both volatile and semi-volatile actives in the topical formulation. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:171 pages:65-72 ispartof: location:England status: published

Reference introduction in thermal desorption with gas chromatography is a critical aspect. It is mostly performed by offline liquid calibration using a micro syringe to inject a liquid standard solution on the sorbent in the thermal desorption tube. This is based on the assumptions that the adsorption-desorption process is quantitative and that no sample is lost in manipulating the tube. However, for analytical procedures involving thermal extraction of solid matrices, the adsorption-desorption processes for sample and reference differ and the assumptions are not always fulfilled. This is explored in this work. First, issues related to the online liquid calibration were investigated. With tubes containing only quartz filters, a relative loss of over 80% was noticed for some solvents due to tube manipulation processes. Enclosing a bed of mesoporous silica as sorbent limited the losses to about 25% when samples were immediately analysed, and even better results were obtained when tubes were stored for several hours so that proper adsorption could take place. An additional sweep gas during loading boosted the transfer of analytes with recoveries above 95%. Next, an inline injection system was installed on the thermal desorber instrument. This sorbent free, independent calibration tool avoids the drawbacks of other approaches. ispartof: JOURNAL OF SEPARATION SCIENCE vol:42 issue:17 pages:2816-2825 ispartof: location:Germany status: published

In this study, a simple and robust capillary electrophoresis method with capacitively coupled contactless conductivity detection (C4D) is developed for the determination of the tetracycline antibiotics (1) tetracycline, (2) chlortetracycline and (3) oxytetracycline. An uncoated, fused silica capillary (60.2 cm long, 75 µm i.d.) and a solution of 50 mM tris(hydroxymethyl) aminomethane, 50 mM l-histidine and 5 mM methyl-β-cyclodextrin, without pH adjustment (pH 8.76), was used as background electrolyte. Electrophoresis at + 25 kV showed a rapid analysis with sufficient resolution among the three antibiotics in the order of tetracycline, chlortetracycline and oxytetracycline. Successive inter-injection rinsing (20 psi) of the capillary ensured intra- and inter-day repeatability (0.9–2.2% RSD and 2.0–4.5% RSD, respectively, for relative peak areas). The method showed satisfactory performance in terms of selectivity, accuracy (99.3–101.4%) and linearity (R2 = 0.999). Finally, the method was applied to commercial samples of tetracycline, oxytetracycline and chlortetracycline. This method can be applied for rapid quality control in developing countries in particular, and across the globe in general.

In this study, an improved liquid chromatographic (LC) method for the analysis of tylosin and its impurities has been developed. A Kinetex EVO C18 column (150 × 4.6 mm, 2.6 μm) packed with superficially porous particles was used as stationary phase. Gradient elution was applied with two mobile phases (A and B) containing acetonitrile, water and 0.2 M ammonium acetate at different ratios (20:10:70 (v/v/v) for A and 60:10:30 (v/v/v) for B). This volatile mobile phase enables the method to be coupled with mass spectrometry (MS) for additional detection and characterization of tylosin impurities. Selectivity, sensitivity, linear calibration, accuracy, precision and robustness of this analytical method were assessed through method validation. In addition, impurities above 0.05% were characterized via LC–MS/MS. It is the first time that a MS compatible method for analysis of tylosin and its impurities is presented. Moreover, it shows a considerably shorter analysis time than previously published methods.

An optimized and economical capillary electrophoretic method for both off-line and on-line study of the enzyme aldehyde oxidase and its substrate phthalazine was developed. The separation of the substrate phthalazine and its metabolite 1-phthalazinone was achieved using micellar electrokinetic chromatography (MEKC) with sodium dodecyl sulphate in the background electrolyte (BGE). The BGE consists of 25 mM sodium phosphate buffer containing 50 mM sodium dodecyl sulphate at pH 7.4. A bare-fused-silica capillary with a capillary length of 40 cm, 50 μm ID and effective length of 30 cm was used to develop the capillary electrophoresis method. Improved separation conditions were elaborated and the separation method was validated based on the ICH and EMA guidelines. The limit of detection for phthalazine and 1-phthalazinone was 8 μM and 3 μM, respectively. The limit of quantification was 25 μM for phthalazine and 10 μM for 1-phthalazinone. The linearity of the detector response was checked for 1-phthalazinone at nine different concentrations in the range 10–500 μM and the determination coefficient was 0.9994. Accuracy was tested by comparing the corrected peak area of 1-phthalazinone reference solution at 20 μM and 50 μM with the corrected peak area of 20 μM and 50 μM 1-phthalazinone in the presence of human liver cytosol (HLC). Accuracy values of +5.3% and -2.5% were obtained at 20 μM and 50 μM, respectively. The on-line enzymatic reaction was successful with the application of the method of transverse diffusion of laminar flow profiles (TDLFP), which enables the mixing as well as separation of the enzyme and substrate inside the nanoliter-scale capillary. TDLFP is examined to be precise when performing 5 consecutive injections, with a relative standard deviation of 7.16% which is within the limitation of EMA standards. This miniaturized and low-cost incubation and separation method could be further introduced into industry and extended to other substrates.

Penicillin G acylase (PGA), as a key enzyme, is increasingly used in the commercial production of semi-synthetic β-lactam antibiotics (SSBAs). With the substitution of conventional chemical synthesis by emerging bioconversion processes, more and more PGAs fermented from different types of strains such as Escherichia coli (E. coli, ATCC 11105), Achromobacter sp. CCM 4824 and Providencia rettgeri (ATCC 31052) have been used in this kind of enzymatic processes. As an intermediate reaction catalyst, PGA protein and its presence in the final products may cause a potential risk of human allergic reaction and bring challenges for both quality and process controls. To achieve qualitative and quantitative analysis of PGAs and their residues in SSBAs, a tryptic digestion coupled with liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was developed and proposed because of advantages like high selectivity and sensitivity. A suitable filter aided sample preparation (FASP) method was also used to remove matrix interference and to enrich the target PGA retained in the ultrafiltration membrane for an efficient enzymatic hydrolysis and subsequent accurate MS detection. Finally, twelve batches of PGAs from eight companies were identified and categorized into two types of strains (E. coli and Achromobacter sp. CCM 4824) using proteomic analysis. In total nine batches of five types of SSBAs (amoxicillin, cephalexin, cefprozil, cefdinir and cefaclor) from eight manufacturers were selected for investigation. Trace levels of PGA residual proteins ranging from 0.01 to 0.44 ppm were detected in six batches of different SSBAs which were far lower than the safety limit of 35 ppm reported by DSM, a manufacturer with expertise in the production of SSBAs by enzymatic processes. The developed FASP with LC-MS/MS method is superior to traditional protein assays in terms of selectivity, sensitivity and accuracy. Moreover, it could provide in-depth analysis of amino acid sequences and signature peptides contributing to assignment of the strain sources of PGAs. This method could become a promising and powerful tool to monitor enzymatic process robustness and reliability of this kind of SSBAs manufacturing.

Aloe leaf latex is a commonly used plant preparation in traditional medicine. However, quality control on the content of medicinally important constituents is often limited. Hence, establishing a reliable quality control method to identify and quantify bioactive markers is important to ensure safety and efficacy. In the present study, a novel liquid chromatographic (LC) method was developed and validated for efficient analysis of bioactive markers to evaluate the quality of aloe leaf latex. Quantification of marker compounds was possible in only 7 min on a monolithic column using gradient elution with 0.1 % formic acid in acetonitrile and water as mobile phases. The major compounds (aloins A and B) could be baseline separated together with related compounds within 10 min. The method showed excellent linearity with determination coefficients (r2) of 0.9999. Detection limits were 0.017 and 0.013 μg/mL, while quantification limits were 0.057 and 0.043 μg/mL for aloin A and aloin B, respectively. Relative standard deviation (RSD) values for intra- and inter-day precision were less than 2% and recoveries for both aloins were close to 100 %. The robustness was evaluated using an experimental design. The method was applied to some aloe leaf latex samples from Ethiopia. Aloin contents varied from 14 to 35 % and two unknown peaks were tentatively identified as aloinoside and microdontin. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:195 ispartof: location:England status: published

Amikacin, gentamicin and tobramycin are aminoglycoside antibiotics mostly used for the treatment of a wide range of aerobic Gram negative bacteria. Lack of a UV chromophore as well as their polar and non-volatile nature make direct determination of these aminoglycosides by conventional LC and GC very challenging. Existing analytical methodology is either expensive, complicated or time consuming. In this work, a thin layer chromatography – flame ionization method was developed for fast analysis of these aminoglycosides in pharmaceutical formulations. Paromomycin was used as internal standard for quantitation. Development of the rod with one single solvent mixture was sufficient to achieve the desired separation of target components. Good determination coefficients (>0.997) were achieved for all target analytes. Repeatability, recovery and detection limits were determined and reported. A total of 5 samples in duplicate can be analyzed simultaneously within 25 s. This method offers the advantage of being able to analyze these aminoglycosides without any need for derivatization or laborious coloration. The developed method was applied to the analysis of some pharmaceutical commercial samples.

The stability of sufentanil-ropivacaine and sufentanil-levobupivacaine solutions was evaluated during 6 months while stored at 4 °C. Containers for sufentanil-ropivacaine were syringe (made of polypropylene (PP)) and cassette (inside bag of polyvinylchloride) and for sufentanil-levobupivacaine syringe (PP) and infusion bag (inner layer of PP). A liquid chromatographic (LC) method was validated and allowed the measurement of the three analytes. Both solutions were found to be stable under the examined conditions with contents that remained close to 100 %.

The threats of substandard and falsified (SF) antimicrobials, posed to public health, include serious adverse drug effects, treatment failures and even development of antimicrobial resistance. Next to these issues, it has no doubt that efficient methods for on-site screening are required to avoid that SF antimicrobials reach the patient or even infiltrate the legal supply chain. This study aims to develop a fast on-site screening method for SF antimicrobials using spectroscopic techniques (mid infrared, benchtop near infrared, portable near infrared and Raman spectroscopy) combined with chemometrics. 58 real-life illegal antimicrobials (claiming 18 different antimicrobials and one beta-lactamase inhibitor) confiscated by the Belgian Federal Agency for Medicines and Health Products (FAMHP) and 14 genuine antimicrobials were analyzed and used to build and validate models.Two types of models were developed and validated using supervised chemometric tools. One was used for the identification of the active pharmaceutical ingredients (APIs) by applying partial least squares-discriminant analysis (PLS-DA) and another one was used for the detection of non-compliant (overdosed or underdosed) samples by applying PLS-DA, k-nearest neighbors (k-NN) and soft independent modelling by class analogy (SIMCA). The best model capable of identifying amoxicillin and clavulanic acid (co-amoxiclav), azithromycin, co-trimoxazole and amoxicillin was based on the mid-infrared spectra with a correct classification rate (ccr) of 100%. The optimal model capable of detecting non-compliant samples within the combined group of amoxicillin and co-amoxiclav via SIMCA showed a ccr for the test set of 88% (7/8) using mid infrared or benchtop near infrared spectroscopy. The best model for detecting non-compliant samples within the group of amoxicillin via SIMCA was obtained using mid-infrared or Raman spectra, resulting in a ccr of 80% for the test set (4/5) and a ccr for calibration of 100%. For the group of co-amoxiclav, the optimal models showed a ccr of 100% for the detection of non-compliant samples by applying mid-infrared, benchtop near infrared or portable near infrared spectroscopy. Taken together, the obtained models, hyphenating spectroscopic techniques and chemometrics, enable to easily identify suspected SF antimicrobials and to differentiate non-compliant samples from compliant ones., info:eu-repo/semantics/published

The conventional approach for residual solvent (RS) analysis is headspace-gas chromatography (HS-GC). This starts from a homogenous sample solution and is based on the equilibrium of the analyte between the sample and the gas phase. Unfortunately, aqueous solutions of albumin form irreversible hydrophobic aggregates when heated above 50 °C. Consequently, the use of HS-GC for RS analysis in albumin becomes problematic due to the presence of an additional solid phase in the HS vial. In this work, a method using a thermal desorber (TD) combined with GC was developed for the determination of RS in drug loaded albumin. Samples were immobilized between two double layers of quartz filter (QF) in a polytetrafluoroethylene (PTFE) insert which was placed in an empty desorption tube prior to TD-GC analysis. The liquid standard mix consisted of ethanol (EtOH), acetone (Ace), dichloromethane (DCM) and chloroform (Chl) dissolved in toluene. Offline liquid calibration (OLC) was applied by introducing 2 μL of the standard mix under counter flow of an inert gas into the TD tube containing a mixed bed of mesoporous silica (MPSi) immobilized between two double layers of QF. The OLC results were verified using the inline liquid calibration (ILC) approach based on a heated GC injector installed on the TD. The validation results revealed that the proposed method has good recovery (> 98 %). R2-values (> 0.998) indicated good linearity over a wide range. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.01 and 0.04 μg on tube, respectively. Repeatability of the method was reported as RSD-values and they were lower than 3 %. A method based on the complete enzymatic digestion of albumin combined with conventional HS-GC was developed to verify the completeness of release of the RS from the albumin. Both the TD-GC and HS-GC methods were applied for the determination of EtOH and DCM in two different albumin samples loaded with experimental drugs. Statistical comparison indicated that there was no significant difference (p > 0.05) between the two methods. However, the HS-GC method following enzymatic degradation is much more expensive and time consuming. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:179 ispartof: location:England status: published

Substandard and falsified (SF) antimicrobials are gaining popularity in both developing and developed countries, posing a growing threat to public health. In general, the evaluation of SF antimicrobial drugs mainly focuses on the identification and quantification of the pharmaceutical active ingredients, ignoring other parameters of drug quality control. This study performed an in-depth characterization and hazard identification of suspected SF antimicrobial medicinal products encountered in Belgium. In this comprehensive evaluation, impurity tests and dissolution studies were carried out. The dissolution profiles of illegal SF antimicrobials were mathematically compared to their genuine counterparts using the f1 and f2 -factor. The results indicated that 17 out of 57 illegal samples contained higher than permitted amounts of impurities and clearly demonstrated low equivalences of dissolution profiles between SF antimicrobials and genuine products. The variations between tablets at the different time points of the dissolution curves were also higher for the SF medicines. Moreover, 11 out of 19 illegal samples failed to meet the dissolution criteria prescribed by the United States Pharmacopeia. As impurities may induce adverse reactions and improper dissolution patterns may be the cause of insufficient drug efficacy, aggravation of illness and even promotion of antimicrobial resistance can be expected. ispartof: DRUG TESTING AND ANALYSIS vol:12 issue:1 pages:53-66 ispartof: location:England status: published

Exocrine pancreatic insufficiency (EPI) can be comfortably diagnosed by a breath test using the mixed triglyceride 2-octanoyl (1–13C)-1,3 distearoyl glycerol (13C-MTG). However, it is not fully accepted as a routine test yet as no vendor provides a certified product for clinical applications. Current recommended methods for quality control of triglycerides are not compatible with the produced expensive small batches of 13C-MTG. In this article, two procedures were miniaturized and optimized: one to confirm the structure by a regiospecific enzymatic reaction and another to check the purity via a methyl esterification. Both pretreated samples were then analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The proposed methods showed good selectivity for the structure confirmation and good linearity with external standards for the purity control: R2 values were higher than 0.995, accuracy was in the 98–100% range and excellent repeatability (RSD

This review describes briefly the high rate of counterfeiting of antimicrobial drugs with focus upon its immediate health consequences. The major part of this review encompasses accounts of the improvements achieved in the domain of miniaturization of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D). The application of this principle into the development of portable devices as well as its application to counter the health-system-crippling phenomenon of counterfeit antibiotic formulations, are discussed in the context of developing countries. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:158 pages:405-415 ispartof: location:England status: published

Concentrated solutions of doxycycline are often added to drinking water of animals for oral antibiotic therapy. However, stability concerns of doxycycline in solution involve an accurate selection of the solvent system to ensure that the active substance will remain within the acceptance range during the product shelf-life and to avoid sub-therapeutic dosage. Different solvent systems have been evaluated in order to determine their influence on the stability of concentrated doxycycline solutions. The results showed differences in the degradation kinetics of doxycycline depending on the co-solvent used and they permitted to select a solvent system for liquid doxycycline hyclate formulations with low rate of degradation even after several months of storage. So, the inclusion of ethanol together with propylene glycol as main excipient was found to be beneficial, while no benefit was observed concerning the addition of citric acid. Once administered to drinking water, the solutions were stable for 24 h with no influence of the solvent system. ispartof: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS vol:159 pages:60-65 ispartof: location:England status: published

A multiple headspace extraction experiment coupled to gas chromatography (MHE-GC) is used for the classification and qualification of different mesoporous silica (MPSi) materials used for drug delivery. In this MHE experiment, a pure liquid solvent probe is fully evaporated in a sealed headspace vial in the presence of the MPSi sample, leading to a gas-solid partitioning that is theoretically described. The obtained results matched with the known characteristics of the studied samples, such as adsorption capacity due to differences in porosity and passivation treatments. Moreover, it proves the effectiveness of a poly dimethyl siloxane (PDMS) coating treatment over a thermal one in reducing the specific interactions of the MPSi. In addition, it evidences the important role of confinement effects when the pore diameter is close to the microporosity range. Finally, a simple experiment for fast screening is proposed by comparison of the results obtained for four different probes used as a mixture.