## 2 Analytical Methods for Phytocannabinoid Profiling
### Instrumental Analysis
#### 2.2.5 Other Analytical Techniques  
* CE is analytical platform used in cannabinoid profiling in only one study [68]. MeCN-based background electrolyte (with 6.5 mM NaOH) in the presence of \(\beta\)-cyclodextrintrin(\(\beta\)CD), improving orthogonal separation media by transiently interacting with compounds based on their geometry and polarity, was used to separate 14 phytocannabinoids (CBG, CBGA, CBD, CBDA, CBN, A\({}^{9}\)-THC, CBC, CBCA, A\({}^{9}\)-THCA, THCV, CBDV and CBGVA) by constant transition between the background electrolyte and \(\beta\)CD. CE performed better than HPLC-DAD in terms of selectivity and runtime, but with significantly lower sensitivity.  
CE's variety, capillary electromatography (CEC), coupling the benefits of CE and HPLC methods, has been used in phytocannabinoid profiling coupled with UV PDA detector in only one study [214]. Baseline separation of seven phytocannabinoids (CBG, CBD, CBN, A\({}^{9}\)-THC, \(\Delta^{8}\)-THC, CBC, \(\Delta^{9}\)-THCA) was achieved by using C\({}_{18}\) column and McN/25 mM phosphate buffer (75:25, _v/v_) as mobile phase for analysis of MeOH/CHCl\({}_{3}\) (9:1, _v/v_) _cannabis_ plant material extracts, while improved sensitivity is achieved using UV cell with extended path length and injection size.  
* NMR Spectroscopy  
NMR-based methods are superior for the purpose of 3D-structure elucidation, especially \(\zeta\)-resolving, \({}^{1}\)H-\({}^{1}\)H COSY and \({}^{1}\)H-\({}^{13}\)C heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC) spectroscopy. The complete \({}^{1}\)H- and \({}^{13}\)C-NMR assignments of the major _Cannabis_ constituents, \(\Delta^{9}\)-THC, \(\Delta^{9}\)-THCA, \(\Delta^{8}\)-THC, CBG, CBN, CBD, CBDA, cannflavin A and cannflavin B have been determined on the basis of one- and two-dimensional NMR spectra, including \({}^{1}\)H- and \({}^{13}\)C-NMR, \({}^{1}\)H-\({}^{1}\)H-COSY, HMQC and HMBC [20]. However, they are seldomly used for quantification purposes, due to the laborious separation and isolation steps required, where significant loss of mass can occur and where there is low sensitivity [4; 215]. Additional issues are the high instrumental costs and necessity of highly specialized personnel. Despite that, NMR is considered as a highly accurate, reproducible and fast technique [1].  
For the purpose of phytocannabinoid profiling, NMR spectroscopy is used as (semi)quantitative method alone [20; 209] or as an orthogonal technique to LC [216; 217; 218] or GC [219] for the purpose of qualitative peak assignment of major phytocannabinoids [20], chemical and morphological examination [220], chemotaxonomic classification [20; 219; 220], metabolomics-based chemovar distinction [51] or quantitative analysis of _cannabis_ plant material without the need of pre-purification step [221], chromatographic separation or use of certified reference standards [219]. Cryogenic NMR spectroscopy combines improved sensitivity and noise reduction with a cryogenic cooling system for the receiver coil and preamplifiers. Its improved spectral quality is employed in compound identification from mass limited samples and as orthogonal analytical technique to HPLC in phytocannabinoid profiling in laser-micro dissected samples of capitate-stalked and capitate-sessile trichomes [220].