Determination of Response Factors for Analytes Detected during Migration Studies, Strategy and Internal Standard Selection for Risk Minimization.

Migration studies are one of the few domains of pharmaceutical analysis employing wide-scope screening methodologies. The studies involve the detection of contaminants within pharmaceutical products that arise from the interaction between the formulation and materials. Requiring both qualitative and quantitative data, the studies are conducted using Liquid Chromatography or Gas Chromatography coupled to a mass spectrometer (LC-MS and GC-MS).

Advantages of automation in plasma sample preparation prior to HPLC/MS/MS quantification: application to the determination of cilazapril and cilazaprilat in a bioequivalence study.

An HPLC/MS/MS method characterized by complete automation and high throughput was developed for the determination of cilazapril and its active metabolite cilazaprilat in human plasma. All sample preparation and analysis steps were performed by using 2.2 mL 96 deep-well plates, while robotic liquid handling workstations were utilized for all liquid transfer steps, including liquid-liquid extraction.

Validation of a novel, fully automated high throughput high-performance liquid chromatographic/tandem mass Spectrometric method for quantification of pantoprazole in human plasma.

An automated high-throughput HPLC/MS/MS method was developed for the quantitative determination of pantoprazole in human plasma. Only 100 microL plasma was placed in 2.2 mL 96 deep-well plates, and both pantoprazole and omeprazole (IS) were extracted from human plasma by liquid-liquid extraction, using diethyl ether-dichloromethane (70:30, v/v) as the organic solvent.

Development and validation of an improved high-throughput method for the determination of anastrozole in human plasma by LC-MS/MS and atmospheric pressure chemical ionization.

In the present study, an automated, 96-well format LC-MS/MS method for the determination of anastrozole in human plasma was developed and fully validated. Within method development procedure, atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) were compared in terms of sensitivity and specificity, with the former proven to be more appropriate and thus being chosen for analyte ionization. In addition, the effect of declustering potential (DP) and collision energy (CE) in sensitivity was, as well, studied and compared between APCI and ESI source employment.

Comparison of hydrophilic interaction and reversed-phase liquid chromatography coupled with tandem mass spectrometric detection for the determination of three pharmaceuticals in human plasma.

In the present study, hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) combined with tandem mass spectrometric detection (MS/MS) were evaluated and compared for the determination of donepezil, cetirizine and loratadine in human plasma, in terms of sensitivity and sample preparation procedure. A retention study for the above compounds of various polarities was performed, using both C(18) and silica columns, with several aqueous-organic mobile phase ratios, in order to investigate their retention mechanism profile under HILIC and RPLC. Both chromatographic conditions were compared for chromatographic analysis of plasma samples processed with a liquid-liquid extraction (LLE) method for donepezil determination, resulting in significantly higher sensitivity under HILIC.

An improved and fully validated LC-MS/MS method for the simultaneous quantification of simvastatin and simvastatin acid in human plasma.

A fully automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of simvastatin (SV) and simvastatin acid (SVA) in human plasma. Plasma samples were treated by acetonitrile (ACN) addition for protein precipitation (PP) and subsequent two-step liquid-liquid extraction (LLE) in 96-deepwell plates, using methyl t-butyl ether (MTBE) as the organic solvent. ACN addition step was proven to enhance method sensitivity, as well as producing cleaner samples for injection.

Validation of a fully automated high throughput liquid chromatographic/tandem mass spectrometric method for roxithromycin quantification in human plasma. Application to a bioequivalence study.

A fully automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for the determination of roxithromycin in human plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2 mL 96-deep-well plates.

Turbulent flow and ternary column-switching on-line clean-up system for high-throughput quantification of risperidone and its main metabolite in plasma by LC-MS/MS: application to a bioequivalence study.

A high-throughput LC-MS/MS method was developed for the simultaneous determination of Risperidone and 9-OH-risperidone in human plasma. A semi-automated sample preparation procedure was applied, including protein precipitation after addition of ACN, via a robotic system, and subsequent sub-zero temperature extraction of the latter. Injections of the ACN extractants were performed on a turbulent flow ternary column-switching system, consisted of dual extraction columns in parallel for on-line purification of samples and an analytical column.

An improved high-throughput liquid chromatographic/tandem mass spectrometric method for terbinafine quantification in human plasma, using automated liquid-liquid extraction based on 96-well format plates.

A fully automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for terbinafine quantification in human plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2 mL 96-deepwell plates.

Simultaneous determination of losartan, EXP-3174 and hydrochlorothiazide in plasma via fully automated 96-well-format-based solid-phase extraction and liquid chromatography-negative electrospray tandem mass spectrometry.

An automated, sensitive and high-throughput liquid chromatographic/electrospray tandem mass spectrometric (LC-MS/MS) assay was developed for the simultaneous determination of losartan (LOS), its major circulating metabolite EXP-3174 and hydrochlorothiazide (HCTZ) in human plasma. LOS and HCTZ coexist in the same drug formulation, and this is the first method that enables the simultaneous determination of both drugs along with the active metabolite of LOS. Since these drugs have different physicochemical properties, the employment of a liquid-liquid extraction (LLE) protocol was precluded.

Quantitative determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry employing an automated liquid-liquid extraction based on 96-well format plates. Application to a bioequivalence study.

An automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for quantitative determination of donepezil in human plasma. 150 MicroL of plasma samples were placed in 2.2 mL 96-deepwell plates and both donepezil and loratadine (IS) were extracted from human plasma by liquid-liquid extraction (LLE), using hexane as the organic solvent.

Application of a semi-automated 96-well format solid-phase extraction, column-switching, fluorescence detection protocol for the determination of alendronate in human urine samples obtained from a bioequivalence study.

In the current study, a semi-automated, 96-well format, solid-phase extraction (SPE), analytical column-switching method for alendronate determination in human urine is developed, validated and applied to a bioequivalence study. The current protocol was a substantial improvement of an existing classical method. A robotic liquid handling system was employed to simplify and reduce the time of sample preparation procedure.

Development and validation of a rapid 96-well format based liquid-liquid extraction and liquid chromatography-tandem mass spectrometry analysis method for ondansetron in human plasma.

A rapid and sensitive LC-MS/MS method for the quantification of ondansetron was developed and validated. The plasma samples were treated by a semi-automated liquid-liquid extraction (LLE) in 1.2 mL 96-well format micro-tubes.

Development of a high-throughput method for the determination of itraconazole and its hydroxy metabolite in human plasma, employing automated liquid-liquid extraction based on 96-well format plates and LC/MS/MS.

A semi-automated liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantification of the antifungal drug itraconazole (ITZ) and its coactive metabolite hydroxyitraconazole (OH-ITZ) in human plasma. The plasma samples underwent liquid-liquid extraction (LLE) in 2.2 mL 96 deepwell plates.

Development of a rapid method for the determination of glimepiride in human plasma using liquid-liquid extraction based on 96-well format micro-tubes and liquid chromatography/tandem mass spectrometry.

A semi-automated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the determination of glimepiride in human plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 1.2 mL 96-well format micro-tubes.