Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography-tandem mass spectrometry.

A method using microextraction by packed sorbent (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) is described for the determination of seven antipsychotic drugs in human plasma. The studied compounds were chlorpromazine (CPZ), haloperidol (HAL), cyamemazine, quetiapine, clozapine, olanzapine (OLZ), and levomepromazine; promazine, protriptyline, and deuterated CPZ were used as internal standards. The validation parameters included selectivity, linearity and limits of detection and quantitation, intra- and interday precision and trueness, recovery, and stability and were studied according to internationally accepted guidelines. The method was found to be linear between the lower limit of quantitation and 1000 ng/mL, except for OLZ and HAL (200 ng/mL), with determination coefficients higher than 0.99 for all analytes, and extraction efficiencies ranged from 62 to 92 %. Intra- and interday precision ranged from 0.24 to 10.67 %, while trueness was within a ±15 % interval from the nominal concentration for all analytes at all studied levels. MEPS has shown to be a rapid procedure for the determination of the selected antipsychotic drugs in human plasma, allowing reducing the handling time and the costs of analysis. Furthermore, GC-MS/MS has demonstrated to be a powerful tool for the simultaneous quantitation of the studied compounds, enabling obtaining adequate selectivity and sensitivity using a sample volume of as low as 0.25 mL.

Determination of piperazine-type stimulants in human urine by means of microextraction in packed sorbent and high performance liquid chromatography-diode array detection.

A method using microextraction by packed sorbent (MEPS) and high performance liquid chromatography-diode array detection (HPLC-DAD) is described for the determination of piperazine-type stimulants in human urine. The studied compounds were 1-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(3-chlorophenyl) piperazine (mCPP) and 1-(4-methoxyphenyl) piperazine (MeOPP); 1-(2-chlorophenyl)-piperazine (oCPP) was used as internal standard (IS). The factors which might influence the extraction were screened previously using the fractional factorial design approach, and none of them influenced significantly the process. The procedure was linear for concentrations ranging from 0.1 (lower limit of quantitation--LLOQ) to 5 µg/mL, with determination coefficients (R(2)) higher than 0.99 for all analytes in all runs. The limits of detection were 0.1 µg/mL for BZP and TFMPP, while for MeOPP and mCPP 0.05 µg/mL was obtained. Intra- and interday precision ranged from 1 to 14%, and accuracy was within a ± 15% interval for all analytes, fulfilling the criteria normally accepted in bioanalytical method validation. Under the optimized conditions, extraction efficiency was higher than 80% for all analytes, except BZP (50%). MEPS showed to be a rapid (<2 min) and simple procedure for the determination of piperazine-type stimulants in human urine, allowing reducing the handling time and costs usually associated to this type of analysis. Furthermore, the fact that only 0.1 mL of sample is required make this method a valuable and powerful tool for drug monitoring in human urine in situations where those compounds are involved, for instance in forensic scenarios.

Determination of biomarkers of tobacco smoke exposure in oral fluid using solid-phase extraction and gas chromatography-tandem mass spectrometry.

A new, simple and sensitive method was described for the simultaneous determination of nicotine, cotinine and trans-3'-hydroxycotinine in oral fluid samples using solid-phase extraction and gas chromatography/tandem mass spectrometry (GC-MS/MS). This technique was developed using only 0.2 mL of sample, and deuterated analogues were used as internal standards. The method was found to be linear between 0.5 and 1000 ng/mL, with determination coefficients higher than 0.996 for all analytes. Intra- and interday precision and accuracy were in conformity with the criteria normally accepted in bioanalytical method validation. All analytes were stable in the samples for at least 24h at room temperature, for at least 72 h at 25°C in processed samples and for at least three freeze/thaw cycles. Absolute recoveries ranged from 89 to 92% for all analytes. GC-MS/MS has demonstrated to be a powerful tool for the simultaneous quantitation of the analytes, providing adequate selectivity and sensitivity. In addition, its performance characteristics allow its routine use in the analysis of biomarkers of tobacco smoke exposure, extending the window of analyte detection in nicotine cessation programs, using a sample amount as low as 0.2 mL of human oral fluid.

Rapid determination of piperazine-type stimulants in human urine by microextraction in packed sorbent after method optimization using a multivariate approach.

This paper describes the analysis of piperazine-type stimulants [1-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP)] in low volume urine samples (0.1 mL) by microextraction in packed sorbent and liquid chromatography-diode array detection. Analyte extraction has been comprehensively optimized, and the influencing factors were screened by means of the fractional factorial design approach. Several parameters susceptible of influencing the process were studied, and these included extraction sorbent type (C(8) and C(18)), sample dilution (1:2 and 1:4), number of aspirations through the device (2 and 8) and the amount of methanol on both the washing (0 and 10%) and eluting solvents (10 and 100%). The method was linear from 0.5 (lower limit of quantitation) to 5 µgmL(-1), with determination coefficients higher than 0.99 for all compounds. Intra- and interday precision ranged from 1 to 9%, trueness was within a ± 11% interval for all analytes, and analyte recoveries were of about 70% for mCPP and TFMPP, and of about 10% for MeOPP and BZP. The method has shown to be selective, as no interferences from endogenous substances were detected by analysis of blank samples, and the analytes were stable in the samples for short periods at room temperature, after three freeze/thaw cycles and in processed samples. Due to its simplicity and speed, this method can be successfully applied in the screening and quantitation of these compounds in urine samples, and is suitable for application in forensic toxicology routine analysis.