[Diagnostic value of a 3D-SPACE-sequence with compressed sensing technology for the knee joint]. / Diagnostische Wertigkeit der 3­D-SPACE-Sequenz mit Compressed-sensing-Technologie am Kniegelenk.

BACKROUND: SPACE (3D fast spin echo acquisition) sequences require long scan times for three-dimensional assessment of acute injury of the knee joint and are flawed due to geometric blurring. Their implementation into routine diagnostic imaging was not feasible until recently. OBJECTIVES: By comparing conventional MRI (magnetic resonance imaging) sequences to 3D (three-dimensional) sequences, it was investigated whether the compressed sensing (CS) technique is inferior to the established 2D sequences with shorter examination times. MATERIALS AND METHODS: A total of 109 patients (age range 18-50 years) with knee injury were examined by MRI between April 2017 and May 2018. The inter- and intraobserver concordance of two blinded readers were assessed. Consensus was achieved in case of discrepancies. Descriptive analyses of absolute and relative frequency and distribution were tested by Fisher's exact test concerning differences between CS-SPACE and standard proton density fat suppressed imaging. RESULTS: Interoberserver concordance (IC) of conventional sequences before/after consensus amounted to 58.8/68.1% (medial meniscus, MM), 68.8/88.7% (lateral meniscus, LM) 88.9/97.2% (anterior cruciate ligament, ACL), 99/100% (posterior cruciate ligament, PCL), 88.9/97.2% (collateral ligament, CL) and chondral injury (CI) 1-2: 64.2%, CI-3: 77% and CI-4: 76%. The IC of CS-SPACE amounted before/after consensus of MM to 50.4/77%, LM 68.8/88%, ACL 89.9/94.5%, PCL 97.2/99.0%, CL 92.6/96.3%. IC of CI was evaluated without consensus and amounted to 65.1% (CI 1-2), 66% (CI 3) and 81.6% (CI 4). CONCLUSIONS: Injuries of ACL, PCL and CL have excellent IC between 3D and 2D sequences. Excellent IC could be found in CI grade 3 and 4 when using 2D sequences and CI grade 4 utilizing CS-SPACE. Our results indicate that CS-SPACE is useful in diagnosing acute knee injuries.

A stability study of amphotericin B, colistin and tobramycin in a hydrophilic suspension commonly used for selective decontamination of the digestive tract by HPLC and in vitro potency measurements.

OBJECTIVES: A suspension for oral use which consists of three non-absorbable antibiotics (amphotericin B, colistin and tobramycin) is often used in clinical practice for the selective decontamination of the digestive tract (SDD) of patients in intensive care. Such a therapy is a preventive tool to minimise the risk of pneumonia and bacteraemia in intubated patients. The administration and the treatment results are controversially discussed. One limiting factor for a unique SDD treatment in the hospitals is a lack of adequate data regarding batch formula and stability for such a formulation. Since no detailed procedures, specifications or stability data are available for manufacturing this formulation there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this research was to collect the physicochemical and microbiological stability data of a developed, stable standard formulation under defined storage conditions. The effectiveness of the SDD suspension should be preferably proven over a long period. This would help guarantee that all patients receive the same preparation, therefore, ensuring similar efficacy and improved safety. METHODS: An adequate formulation composed of the registered, marketed medicinal product Ampho-Moronal suspension (Dermapharm AG, Germany) and a buffered, preserved aqueous solution of colistin and tobramycin both as sulfates has been developed. A stability study has been performed on two batches of the formulation. During the storage, samples were taken and compatibility was verified by physicochemical and microbiological testing in stability-indicating terms of colour, odour, flavour, pH, chemical and microbiological purity as well as in vitro potency. The test methods were built and tailored to be suitable, reliable and precise for the test needs. RESULTS: The results show the physicochemical and microbiological stability of the described formulation for defined storage conditions. CONCLUSIONS: A standardised formulation with a proven stability for at least 6 months under fridge (5°C±3°C) conditions for the SDD of patients in intensive care was established.

Purity determination of amphotericin B, colistin sulfate and tobramycin sulfate in a hydrophilic suspension by HPLC.

A suspension comprising of the three antibiotic substances amphotericin B, colistin sulfate and tobramycin sulfate is often used in clinical practice for the selective decontamination of the digestive tract of patients in intensive care. Since no detailed procedures, specifications or stability data are available for manufacturing this suspension, there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this work is to develop a standardized formulation and to determine its stability under defined storage conditions. This would help guarantee that all patients receive the same preparation, therefore ensuring similar efficacy and improved safety. The first step in this process is to develop the required analytical tools to measure the content and purity of the drug substances in this complex mixture. In this paper, the development and validation of these tools as well as the development of the drug suspension formulation is described. The formulation comprises of Ampho-Moronal(®)-Suspension (Dermapharm) and a buffered, preservated aqueous solution of colistin sulfate and tobramycin sulfate. Two simple, well established high-performance liquid chromatography (HPLC) methods in the European Pharmacopoeia (EP) for impurity profiling of the two active ingredients amphotericin B and colistin sulfate were combined with a newly developed sample extraction procedure for the suspension. Sufficient selectivity and stability-indicating power have been demonstrated. Additionally, a new robust routine method was developed to determine possible degradation products of tobramycin sulfate in the investigated suspension. The specificity, precision, accuracy and linearity of the analytical procedures were demonstrated. The recovery rate was in the range of 90-110%. The precision results for the calculated impurities showed variation coefficients of <10%. The calibration curves were found to be linear with correlation of greater than 0.9994 for all components. The results show the suitability of the methods for the quality control analysis of the suspension.