Ketamine R,s Structure

3.1 Chiral recognition in Ketamine by Mass Spectrometry

3.1.1 Drug introduction

Ketamine, the brand name Ketalar, is a drug mainly used for starting and maintaining anesthesia (2). It induces a trance-like state while providing pain relief, sedation, and memory loss (3). It can also be used in treat chronic pain and provide sedation in intensive care (4,5). It generally plays a role in heart function, breathing, and airway reflexes (3). Effects normally begin within five minutes when given by injection with the main effects lasting up to 25 minutes (1,2).

[pic 1]

Figure 1 Ketamine Hydrochloride Injection, USP, CIII Class: General Anesthetic. Generic Name: Ketamine Hydrochloride Injection, USP Brand Name: Equivalent Ketalar. Control Class: Class III) (11)

Ketamine (2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone) is an arylcycloalkylamine structurally related to phencyclidine (PCP).The free base of ketamine is showed in Figure 2. And the molecular formula for the free base is C13H16ClNO and the hydrochloride salt formula is C13H17Cl2NO. The molecular weight of free base is 237.73 g/mol, hydrochloride salt is 274.18 g/mol. The melting point is 92-93°C (free base) and 262-263°C (hydrochloride salt)

[pic 2]

Figure 2 The Chemical Structure of the free base of ketamine.(12)

Ketamine acts as an NMDA receptor antagonist, but also perform as a ligand on opioid receptors and as monoamine transporters among others (8). Ketamine hydrochloride is soluble in water. It is white crystalline powder and has a pKa of 7.5 (13). The commercially available pharmaceutical form is an aqueous solution for injection of the racemic mixture of the hydrochloride salt. The history of Ketamine traced back to 1962 when it was first synthesized by American scientist Calvin Stevens at the Parke Davis Laboratories (1). It is one of the Essential Medicines definite by the World Health Organization , listed as the most important medications needed in a basic health system (9).The average price of ketamine is around 35USD per gram (10).

3.1.2 Mass spectrometry chiral recognition mechanisms

MS usually combine with many other enantioselective techniques to identify analytes. It is a new way to analyze chiral substance, which greatly increases the sensitivity and accuracy of the analytical methods (14).

There are mainly two choices for chiral analysis using hyphenated MS techniques: the direct and indirect approaches.

In the indirect approach, the drug enantiomers are formed into a pair of covalent diastereomeric complexes which derivatized from an enantiopure chiral reagent known as the “chiral derivatization reagent”. These complexes can be separated by many conventional methods due to the reason that they have different physical and chemical properties.