The introduction of Quality by Design (QbD) in Drug Development has resulted in a greater emphasis on chemical process understanding, in particular on the origin and fate of impurities. Therefore, the identification and quantitation of low level impurities in new Active Pharmaceutical Ingredients (APIs) play a crucial role in project progression and this has created a greater need for sensitive and selective analytical methodology. Consequently, scientists are constantly challenged to look for new applications of traditional analytical techniques. In this context a normal-phase liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method was developed to determine the amount of a de-fluorinated analogue impurity in Casopitant Mesylate, a new API under development in GlaxoSmithKline, Verona. Normal-phase LC provided the selectivity needed between our target analyte and Casopitant, while a single quadrupole mass spectrometer was used to ensure the sensitivity needed to detect the impurity at <0.05%w/w. Standard solutions and samples were prepared in heptane/ethanol (50:50, v/v) containing 1% of 2 M NH(3) in ethanol; the mobile phase consisted of heptane/ethanol (95:5, v/v) with isocratic elution (flow rate: 1.0 mL/min, total run time: 23 min). To allow the formation of ions in solutions under normal-phase (apolar) conditions, a post-column infusion of a solution of 0.1% v/v of formic acid in methanol was applied (flow rate: 200 microL/min). The analysis was carried out in positive ion mode, monitoring the impurity by single ion monitoring (SIM). The method was fully validated and its applicability was demonstrated by the analysis of real-life samples. This work is an example of the need for selective and accurate methodology during the development of a new chemical entity in order to develop an appropriate control strategy for impurities to ultimately ensure patient safety.

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When designing a hydraulic fracturing intervention, the selection of the interval to be perforated is critical in order to maximize oil production and to avoid unwanted gas/water breakthrough from neighboring layers.While on new wells the perforation interval can be selected carefully analyzing logs and CBL, it can be challenging to design a workover where the HF targets a zone that is right in the middle of a large existing perforated interval (125 meters).Leaving exposed too many perforations during a fracturing treatment could result in operational issues such as early screenout and/or uncertainties on the fracture initiation point. Zonal isolation could be obtained by cementing part of the perforations but this would mean in permanently losing part of the level. This paper will describe a successful workover carried on a shut-in oil well, onshore Congo, where a single stage fracturing treatment was performed leaving exposed only few meters of the existing perforations and without permanently losing the remaining intervals.This result was obtained using a multi-stage ball drop frac completion setting the packers across the perforated interval. The downhole equipment was able to withstand the treating pressure during the fracturing treatment and production was obtained through the frac sleeves.This workover resulted in a significant oil production from a well that never produced until that moment.