Bioanalytical methods for the determination of antipsychotic drugs

Abstract

Antipsychotic drugs are popular for the treatment of schizophrenia and other psychoses. In general, antipsychotics are administered in oral doses of only a few milligrams per day and they are widely metabolized in the body. Therefore, the concentration of these drugs in plasma is very low (pg-ng/mL levels). In addition, therapeutic drug monitoring (TDM) of antipsychotic drugs has proven to be of notable value for determining poor compliance of patients and addressing the challenges associated with considerable genetic variability in their metabolism. Thus, in order to conduct pharmacology and toxicology studies and clinical TDM of antipsychotics, as well as address the challenges associated with polypharmacy and drug metabolism, highly sensitive, selective and accurate bioanalytical methods are essential. The most recent studies on the determination of antipsychotics will be reviewed, including separation techniques, sample pretreatment, detectors and validation.

Chlorpromazine quantification in human plasma by UPLC–electrospray ionization tandem mass spectrometry. Application to a comparative pharmacokinetic study

“…The biological concentration of chlorpromazine and other antidepressants has been assessed in human urine, serum, rat plasma and brain tissue using several analytical methods, mainly LC-MS/MS [25][26][27], GC-MS [9] and HPLC-UV [28]. Some of these methods also applied liquid-liquid extraction using isopropyl ether [27] or t-butyl ethyl ether [14], while other used a protein precipitation with a mixture of acetonitrile/methanol [25].…”

“…The LC-MS/MS is the method of choice for the bioanalysis of organic molecules from complex biological matrices since the mid 90s [19][20][21][22][23][24]. To date, very few LC-MS/MS methods have been reported for the quantification of chlorpromazine in plasma [25][26][27].…”

Analytical Techniques and Quality Control of Pharmaceuticals

“…This hyphenated system can also provide a rapid means to immediately and accurately determine whether the drug meets the regulatory acceptance criteria. All impurities, including water and organic solvents, present at significant amounts, are accurately measured [23].MS instruments are characterized by three distinct features, namely: (i) the source where the analyte is first ionized, generally through electron ionization (EI) or atmospheric pressure ionization (electrospray ionization, ESI); (ii) the analyzer, where ions of discrete mass-to-charge ratios (m/z) are separated and focused by the mass screen system; (iii) the actual mass detector;…”

“…Many high-detection power LC-MS or LC-MS/MS methods for the bioanalysis of antipsychotics have been published [23][24][25].…”

Validated GC/MS method for the simultaneous determination of clozapine and norclozapine in human plasma. Application in psychiatric patients under clozapine treatment

“…A recent review provides sufficient information regarding the published methods in the literature for the determination of CLZ and NCLZ [10]. Three LC methods [11][12][13] have been reported using single quadruple MS detector for the determination of these analytes.…”