Analysis of Cannabinoids Concentration in Cannabis Oil Galenic Preparations: Harmonization between Three Laboratories in Northern Italy

Abstract

Medical cannabis is increasingly being used in the treatment and support of several diseases and syndromes. The quantitative determination of active ingredients (delta-9 tetrahydrocannabinol, THC, and cannabidiol, CBD) in galenic oily preparations is prescribed by law for each produced batch. The aim of this work is to describe the organization of the titration activity centralized at three regional reference laboratories in Northern Italy. Pre-analytical, analytical, and post-analytical phases have been defined in order to guarantee high quality standards. A cross-validation between laboratories allowed for the definition of the procedures that guarantee the interchangeability between reference laboratories. The risk management protocol adopted can be useful for others who need to undertake this activity.

Analytical Techniques for Phytocannabinoid Profiling of Cannabis and Cannabis-Based Products—A Comprehensive Review

“…Most of the mobile phases used in HPLC/DAD analysis of phytocannabinoids consisted of buffered aqueous solutions of ammonium acetate [ 176 ], ammonium formate [ 83 , 142 ], formic acid [ 11 , 40 , 50 , 60 , 61 , 62 , 63 , 78 , 173 , 177 , 178 , 179 , 180 , 181 , 182 ], acetic acid [ 19 , 183 , 184 ], o -phosphoric acid [ 165 , 185 ] or 5% MeCN/80% MeCN with 0.1% o -phosphoric acid [ 69 ]. Acidic conditions are preferred for cannabinoid acids (Δ 9 -THCA, CBDA, CBGA).…”

“…Binary mobile phase system consisted of H 2 O/MeOH (10:90, v/v ) [ 186 ], H 2 O/MeOH (17/83, v/v ) [ 187 ] and H 2 O + 0.1% formic acid/MeOH + 0.1%; formic acid is most commonly used for phytocannabinoid profiling [ 11 , 63 , 65 , 147 , 185 , 188 ]. Other binary systems that provide good peak shape and improved resolution are also used, such as H 2 O + 0.1% formic acid/MeCN + 0.1% formic acid [ 40 , 55 , 64 , 80 , 109 , 134 , 144 , 182 , 183 , 185 , 188 , 189 ], H 2 O + 0.1% TFA/MeOH + 0.1% TFA [ 68 ], MeCN/H 2 O (75:25, + 0.05% formic acid, v/v )/isopropanol:MeCN (80:20 + 0.05% formic acid, v/v ) [ 183 , 184 ], 5% MeCN + 0.1% formic acid/MeCN + 5% H 2 O + 0.1% formic acid [ 78 ], H 2 O + 0.1% formic acid/MeCN [ 27 , 63 , 185 ], 5% MeCN + 0.1% formic acid/80% MeCN + 0.1% formic acid [ 69 ] and MeCN/H 2 O + 0.85% phosphoric acid [ 42 ].…”

“…Only one methods use direct injection [ 184 ], bypassing the column. Most of the published methods employ columns with normal phase C 18 stationary phase (Ascentis Express C 18 [ 40 , 178 ], Luna C 18 [ 69 , 177 ], Kinetex C 18 [ 11 , 19 , 71 ], Luna Omega Polar C 18 [ 58 , 114 , 118 , 139 ], Luna Omega PS C 18 [ 27 ], XTerra MS C 18 [ 83 ], Acquity UPLC BEH C 18 [ 181 ], Acquity BEH Shield RP18 [ 144 ], MacMod ACE5 C 18 -AR [ 190 ], ACE 3 C 18 -PFP [ 187 ], ACE Excel 3 C 18 [ 111 ], Poroshell 120 SB-C 18 [ 182 ], Poroshell 120 EC-C 18 [ 188 , 189 ] or 120 SB-C 18 [ 34 , 35 , 36 , 38 ], Shim-pack XR-ODSII RP C 18 [ 149 ], Nucleodur ® C 18 Gravity [ 185 ], Zorbax Eclipse Plus C 18 [ 92 , 183 ], Zorbax Eclipse XDBC 18 [ 186 ], Zorbax SB-C 18 [ 133 ], Atlantis T3 C 18 [ 42 ], with [ 11 , 19 , 34 , 35 , 36 , 38 , 83 , …”

Innovative Clinical-Organizational Model to Ensure Appropriateness and Quality in the Management of Medical Cannabis: An Italian Regional Case

“…This shift can be explained by the advantages of the oil: a greater simplicity of management that allows patients to take a more precise and accurate dosage of the active ingredients (THC and CBD), compared to solid preparations, and greater compliance by patients themselves. Each oily preparation is in fact subjected to titration; this procedure quantifies the main active ingredients (THC, THCA, CBD, CBDA) contained in the preparations [35][36][37]. Unlike paper preparations and/or granules, it is not possible to trace their concentration, not only in the different dosage units, but also in the decoction that the patient makes for his/her own intake.…”

“…Unlike paper preparations and/or granules, it is not possible to trace their concentration, not only in the different dosage units, but also in the decoction that the patient makes for his/her own intake. Each oily preparation is in fact subjected to titration; this procedure quantifies the main active ingredients (THC, THCA, CBD, CBDA) contained in the preparations [35][36][37]. Unlike paper preparations and/or granules, it is not possible to trace their concentration, not only in the different dosage units, but also in the decoction that the patient makes for his/her own intake.…”