Cyclizine (CYZ), 1-benzhydryl-4-methylpiperazine or 1-(diphenylmethyl)-4-methylpiperazine, is a piperazine derivative which has been competently indicated for the preclusion and therapy for nausea and vomiting linked to motion sickness Fig. 1 . It is an antihistaminic drug with sedative effect besides having H1 antagonist activity with central anti-muscarinic action . Typically CYZ is administered post-operatively as an anti-emetic drug, but it is considered to have potential for addiction and hallucinogenic effects .
Lately, teenagers or patients with cancer in the inpatient unit of major cancer centers have misused CYZ in large doses intravenously (IV) . Many cases of CYZ dependency were found in people with conventional types of recreational drug abuse, but long-term opiates are reported in patients with chronic pain of uncertain origin. Abuse of CYZ has been documented for more than 40 years, but these concerns are not commonly recognized . There are many side effects of overdose and illegal use of CYZ. The most frequently described symptoms were confusion, hallucinations, disorientation, tremors, drowsiness, dysarthria, chest pain, ataxia, seizures, as well as lead to suicide .
Cyclizine dependence also reported in patients with complex nutritional problems . According to British Pharmacopoeia (BP), it has two impurities; impurity A named 1-Methylpiperazine (MPZ) and impurity B named Diphenylmethanol (DPM) or benzhydrol Fig. 1. Both impurities are harmful, toxic, and dangerous to human bodies when CYZ parenteral formulations are given intravenously. They result in respiratory failure as well as damage to a variety of target organs [7, 8].
A literature review revealed that several approaches to the determination of CYZ have been identified, either in the formulation of raw materials or pharmaceuticals, either alone or in conjunction with other medications. These recorded analytical approaches include non-aqueous titration , spectrophotometric [9–11], TLC-densitometric [12–14], HPLC [15–20], capillary zone electrophoretic , and potentiometric [22– 25] methods. Neither in its pharmaceutical formulation nor in biological fluids, have no spectrofluorimetric methods for determining CYZ been published.
In analytical chemistry, fluorescence is the most widespread and useful form of photoluminescence . Spectrofluorimetric analysis was conducted because of its high level of sensitivity, selectivity, simplicity, and low cost as compared to other chromatographic methods, unlike the spectrofluorimetric system, which can scan a large number of samples in a shorter amount of time, chromatographic methods are constrained by the number of samples that can be processed in one working day .
Pharmacokinetic parameters like absorption, distribution, metabolism, excretion and toxicity (ADMET) profiling of compounds were studied by the pkCSM ADMET descriptors algorithm protocol . In silico study means that this study conducted on computer or via computer simulation. It has many advantages in lowering the need for costly laboratory work and clinical trials for either drug discovery or ADMET predictions. In silico methods in ADMET-associated predication have many applications in estimate aqueous solubility, pKa, blood- brain barrier and CNS permeation .
This work aims to establish a new, selective, simple and highly sensitive spectrofluorimetric approach for the analysis of CYZ in the presence of its toxic impurities or in biological matrices. The developed method was effectively employed for analysis of CYZ in its parenteral preparation and human plasma which allow its application for routine quality control analysis dependent on its natural fluorescence. Additionally, prediction the pharmacokinetic parameters of CYZ in human plasma and its two impurities were conducted by using in silico study and ADMET predictions.