A Novel Triple Stage Ion Trap MS method validated for curcumin pharmacokinetics application: A comparison summary of the latest validated curcumin LC/MS methods

Abstract

Even through more sensitive methods for quantifying trace levels of curcumin in plasma were urgently needed, beyond tandem mass spectrometry, the Paul trap MS/MS/MS has never been tested for curcumin quantification. Because of its unique trap function to accumulate target compounds selectively by optimizing multiple stage MS experiments, it showed great potential to remove background issues reported at low concentration ranges. A novel Triple stage Ion Trap Mass Spectrometry coupled with High Performance Liquid Chromatography (HPLC-ITMS/MS/MS) method has been developed and validated as a curcumin quantification method, for the first time. The use of isotope labeled curcumin-d6 as a novel internal standard (IS) is suggested and tested according to FDA validation procedure. A simplified sample preparation is introduced and validated by coupling a novel acetonitrile precipitation with molecular weight cut-off size exclusion method. This method demonstrated excellent recovery rate of 96.69%-109.26% and minimum matrix effect of 95.40%-110.98%. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for curcumin in rat plasma were 0.1 ng/ml and 1 ng/ml respectively. The linear calibration curve for quantifying curcumin in rat plasma was 1-3000 ng/ml (r > 0.99) with intra-day and inter-day RSD and accuracy within ±5.11%. Its application in a Pharmacokinetics (PK) study demonstrated detection of curcumin at a very low plasma level (1.0 ng/ml) and it would be applied to larger sample size animal and clinical pharmacokinetic studies. The presented ITMS/MS/MS quantification method has shown its advantages, including better sensitivity, accuracy, precision, wider calibration range and simplicity in sample preparation, when comparing with other curcumin LC/MS analysis methods in the latest 4 years.

Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects

“…Sensitive, accurate, and robust analytical methods are required for CUR quantification because a) CUR levels in plasma/serum/tissues are low due to poor bioavailability, rapid metabolism, and degradation, b) matrix interferences, and c) proper evaluation of bioefficacy and understanding mechanism/mode of action [7,26].…”

“…Hence, an ideal sample preparation method should be simple, fast, and yielding maximum analyte recovery efficiently and minimum (or no) matrix interferences. Table 2 shows various sample preparation protocols used for extraction and analysis of curcuminoids from a wide array of matrices (biological-plasma and tissue, plant -rhizome and foods) as well as different formulations [13,25,26,27,28,29,31,32,33,35,36,37,38,39,130,131].…”

“…After protein precipitation, the resulting solution was centrifuged, the supernatant was collected, dried under nitrogen and reconstituted in an appropriate solvent for analysis. Similarly, Li et al used acetonitrile protein precipitation, followed by size-exclusion chromatography [26]. After the protein precipitation, the resulting mixture was centrifuged, and the supernatant was transferred to an OMEGA NANOSEP 10K nanosep size-exclusion tube.…”

“…Different sample preparation and analytical techniques have been developed to analyze CCMs [25,26], however, often detailed optimization information is not presented. It is essential to understand how different sample preparation and analysis techniques impact the quantification, bioavailability, pharmacokinetic profiles, and clinical efficacy of CCMs [25,26,27,28,29,30,31,32,33], which in turn will assist in increasing understanding of curcuminoids as a potential therapeutic agent [7,26,31,34].…”

“…Different sample preparation and analytical techniques have been developed to analyze CCMs [25,26], however, often detailed optimization information is not presented. It is essential to understand how different sample preparation and analysis techniques impact the quantification, bioavailability, pharmacokinetic profiles, and clinical efficacy of CCMs [25,26,27,28,29,30,31,32,33], which in turn will assist in increasing understanding of curcuminoids as a potential therapeutic agent [7,26,31,34]. This review presents current research updates in the areas of CCMs formulations, and their clinical outcomes [6,14,19,20,21], sample preparation [25,26,27,28,29,31,32,33,35,36,37,38,39], and various methodologies used to analyze CCMs [25,26,33,38,39,40,41,42,43,44,45,46,47,48,49].…”