Serum and Saliva Concentrations of Venlafaxine, O-Desmethylvenlafaxine, Quetiapine, and Citalopram in Psychiatric Patients

2018

Molecules

Saliva is far less popular as a diagnostic material than blood. This has resulted in a lack of procedures for the sampling and handling of saliva, e.g., effective ways to purify endogenous compounds from saliva to enable a simultaneous determination of xenobiotics such as neuroleptics. Therefore, the aim of this study was to develop an analytical procedure to purify saliva samples so that it is then possible to simultaneously determine five neuroleptics (aripiprazole, clozapine, olanzapine, quetiapine and risperidone) and the antiepileptic drug carbamazepine, and their respective metabolites (dehydroaripiprazole, N-desmethylclozapine, N-demethylolanzapine, norquetiapine, 9-OH-risperidone and carbamazepine-10,11-epoxide). A study of three types of solid-phase extraction (SPE) columns showed that the purest eluates were obtained using columns containing ion exchange sorbent. The sorbents were first washed with water then with a mixture of water and methanol (1:1), and the adsorbed residue was eluted with a 5% ammonia solution in methanol. Saliva samples for SPE were diluted with 2% formic acid and a mixture of methanol and water (1:1). This procedure was developed to purify a saliva sample spiked with a mixture of neuroleptics and carbamazepine, and their respective metabolites. A chromatographic analysis confirmed the isolation of all compounds, indicating that this procedure can be used in further development and validation for a method designed to monitor the levels of neuroleptic drugs in saliva and to monitor their uptake by patients.

Section: Introductionmentioning

confidence: 60%

Solid Phase Extraction Purification of Saliva Samples for Antipsychotic Drug Quantitation

2018

Molecules

“…Frequently, the analysis was carried out using liquid chromatography coupled with MS detection. Due to the high sensitivity, LC-MS allows an LOQ of several ng/mL [8,9,16,17,18,19,20,21,22,23] and in some cases below 1 ng/mL [12,13,24,25,26,27]. In the analysis of psychoactive compounds among other neuroleptics using HPLC with UV or DAD detection, the LOQ was much worse, at the level of several or even 20 ng/mL [4,11,28].…”

Section: Resultsmentioning

confidence: 99%

“…For example, saliva has been proven useful in monitoring therapy using carbamazepine. The potential of saliva as a biological material to monitor the concentration of drugs in the body was also determined for antipsychotics, namely, quetiapine [8,9,10], clozapine [10,11], and risperidone [10,12,13,14,15]. The data in the literature indicate that analytes are usually determined using liquid chromatography with UV detection [4,5,11,15], mass spectrometry [8,9,10,12,13] or coulometry [14].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Quantification of Antipsychotic and Antiepileptic Drugs and Their Metabolites in Human Saliva Using UHPLC-DAD

2019

Molecules

Neuroleptics and antiepileptics are excreted in saliva, which can, therefore, be very useful in determining their concentration in the body. This study presents a method developed to simultaneously identify five neuroleptics—olanzapine, quetiapine, risperidone, aripiprazole, and clozapine—and the antiepileptic carbamazepine together with their metabolites: N-demethyl olanzapine, norquetiapine, 9-OH-risperidone, dehydroaripiprazole, N-desmethylclozapine, and carbamazepine-10,11 epoxide. Chlordiazepoxide was used as the internal standard. Strata-X-C columns were used for isolation of the compounds. Chromatographic analysis was carried out using UHPLC with a diode array detector (DAD). A mixture of acetonitrile and water with the addition of formic acid and 0.1% triethylamine was used as the mobile phase. The developed method was validated by determining the linearity for all analytes in the range 10–1000 ng/mL and the value of R2 > 0.99. Intra- and inter-day precision were also determined, and the relative standard deviation (RSD) value in both cases did not exceed 15%. To determine the usefulness of the developed method, saliva samples were collected from 40 people of both sexes treated with the tested active substances both in monotherapy and in polypragmasy. In all cases, the active substances tested were identified.

“…This strong correlation may indicate a potential benefit of determining and monitoring changes in saliva quetiapine levels. Some literature data indicate a correlation of quetiapine concentration in saliva and blood, which indicates that saliva could be used to monitor quetiapine levels and its metabolisms [ 19 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Both substances, free fraction and metabolite, are present in saliva. Usually, there is a correlation between the drug concentration in blood and saliva, and there is one available study that confirms it for quetiapine [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Age, Drug Dose, and Sampling Time on Salivary Levels of Olanzapine, Quetiapine, and Their Metabolites

2020

JCM

Although blood is the basic test material to monitor levels of antipsychotic drugs in a person’s system, saliva could serve as a more convenient test material. Therefore, the aim of this novel study was to determine the correlations between the salivary levels of olanzapine and quetiapine (and their metabolites: N-demethyl olanzapine and norquetiapine) and the patient’s sex and age, dose level, and the time of sampling. The study involved two groups of patients: 21 female patients starting treatment immediately after being admitted to the hospital and 36 male and female nursing home residents, long-time users of the studied drugs. Women had lower levels of the tested analytes than men. Quetiapine levels in the saliva of people starting the treatment showed a positive correlation with the age of the patients and a strong positive correlation with the dose level. The saliva levels of olanzapine showed a strong correlation with its metabolite in patients who had recently started treatment. Among long-time users of this drug, salivary levels differed significantly before and after administration. In conclusion, the results indicate that there is a possibility of using saliva as a material for monitoring quetiapine or olanzapine concentrations, especially in people starting treatment.