Classification of the ibuprofen active pharmaceutical ingredients by chemical patterns combining HPLC, 1H-NMR spectroscopy and chemometrics: traceability of legal medicines.

INTRODUCTION: Ibuprofen is one of the widespread used non-steroidal anti-inflammatory drugs. Ibuprofen active ingredient is manufactured in many sites located all around the world. The aim of this paper was to classify the geographical source of ibuprofen active pharmaceutical ingredients (APIs) from the legal market, based on chemical characteristics and its impurity pattern and to define a geographical fingerprint. METHODS: To classify ibuprofen in different geographical groups, the chemometrics by principal component analysis (PCA) and Cluster analysis was applied to HPLC, 1H-NMR data of twenty-four samples of APIs from approved manufacturers located in different European and Asian countries. RESULTS: The PCA showed clearly two different geographical groups, based on particular patterns of European or Indian samples; the cluster analysis showed the similarity of group. CONCLUSION: The chemometric analysis is an important tool for tracking the geographical origin of APIs. This could be useful to supplement the quality control ensuring safety of the medicinal products in legal market and dealing with the evolving changes of the illegal market.

Quantitative analysis of iobitridol in an injectable preparation by 1H NMR spectroscopy.

Nuclear magnetic resonance spectroscopy was used for direct quantitative determination of iobitridol in an injectable formulation. The method was developed on a medium field strength magnet (400MHz) and validation was performed by assessing specificity, accuracy, precision, linearity, stability of samples and robustness. Validation data confirm that the method is highly appropriate for direct quantification of iobitridol in the final formulation. Moreover the method has a good potential for rapid screening analyses due to straightforward experimental setup and lack of any sample pretreatment.

LC-MS Determination of remifentanil in maternal and neonatal plasma.

An HPLC-MS with electrospray ionization method for the determination of remifentanil in human plasma samples, pre-treated with SPE cartridge, has been developed and validated. Ionisation was performed by positive-ion electrospray and quadrupole filter mass spectrometer operated in the single ion-recording mode. Pre-treatment was performed using Waters Oasis((R)) SPE cartridges. Chromatographic separation was achieved in isocratic elution using a X-Terra C8 5 microm, 150 mm x 2.1 mm i.d. column. The mobile phase consisted of a mixture of water, methanol and acetonitrile (86:10:4, v/v/v) containing 0.1% of formic acid. The method showed to be linear in the range between 0.5 and 48.0 ng/ml, the estimated LOD is 0.18 ng/ml and the LOQ is 0.5 ng/ml. The method can be used to quantify remifentanil in plasma samples taken from adult and newborn patients in a range suitable for clinical studies.

LC-MS determination of MPTP at sub-ppm level in pethidine hydrochloride.

An HPLC-MS with electrospray ionisation method for the determination of MPTP at sub-ppm level in pethidine hydrochloride has been developed and validated. Ionisation is performed by positive-ion electrospray and the quadrupole filter mass spectrometer is operated in the single ion recording mode. Chromatographic separation was achieved in gradient elution using a symmetry C18, 5 microm, 150 mm x 2.1 mm i.d. The mobile phase comprised water containing 0.1% formic acid (v/v) and acetonitrile containing 0.1% formic acid (v/v). The method showed to be linear in the range between 0.2 and 2.2 ng/ml, the estimated LOD was lower than 0.1 ng/ml and the LOQ was lower than 0.2 ng/ml.