An experimental design approach using response surface techniques to obtain optimal liquid chromatography and mass spectrometry conditions to determine the alkaloids in Meconopsi species

A statistic approach using response surface methodology (RSM) for optimization of the ultra-high performance liquid chromatography (UHPLC) gradient and ionization response of electrospray ionization mass spectrometry (ESI-MS) to analyze the main alkaloids from the plant matrices of six Meconopsi species is presented. The optimization was performed with Box–Behnken designs (BBD) and the multicriteria response variables were described using global Derringer's desirability. Four parameters of UHPLC and six major parameters of ESI-MS were investigated for their contribution to analytes separation and response, leading to a total of 27 and 54 experiments being performed for each instrument, respectively. Quantitative analysis of four main alkaloids in nine samples from six Meconopsis species was employed to evaluate the statistical significance of the parameters on UHPLC–QTOF/ESI-MS analytes response. The results indicated that the optimized UHPLC–QTOF-MS method is very sensitive with the limit of detections (LODs) ranging from 0.5 to 0.1 ng/ml. The overall intra-day and the inter-day variations were less than 2.45%. The recovery of the method was in the range of 94.3–104.8% with RSD less than 4.0%. This approach has important implication in sensitivity enhancement of the ultra-trace determination of alkaloids from complex matrixes in the fields of natural products, metabolomics and pharmacokinetics.