A highly sensitive LC–MS–MS assay for analysis of midazolam and its major metabolite in human plasma: Applications to drug metabolism

Jabor, Valquíria Aparecida Polisel; Coelho, Eduardo Barbosa; Santos, Neife Aparecida Guinaim dos; Bonato, Pierina Sueli; Lanchote, Vera Lúcia

doi:10.1016/j.jchromb.2005.05.011

Cited by 44 publications

(44 citation statements)

References 20 publications

(27 reference statements)

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“…The optimal LC conditions described above permitted a typical analysis cycle time of less than 4.3 min, during which midazolam, 1′-hydroxymidazolam and triazolam were separated as symmetric peaks eluted from the LC column in the order of triazolam (2.1 min), 1′-hydroxymidazolam (2.3 min) and midazolam (2.5 min). This run time is much shorter than previously described (Jabor et al, 2005;Lepper et al, 2004;Marquet et al, 1999;Quintela et al, 2004;Shiran et al, 2003).…”

Section: Lc-ms/msmentioning

confidence: 63%

“…In recent years, liquid chromatography-mass spectrometry (LC-MS) methods have been widely employed in bioanalytics for better sensitivity and higher throughput. Several related methodologies have been published with a lower limit of quantification (LLOQ) of down to 0.1 ng/mL when 200 µL of human plasma was used (Kanazawa et al, 2004;Jabor et al, 2005;Lepper et al, 2004;Marquet et al, 1999;Quintela et al, 2004;Shiran et al, 2003). However, the reported LC-MS/MS run time was still up to 15 min (Quintela et al, 2004), which limits the analysis throughput when large-scale clinical samples need to be assayed.…”

Section: Introductionmentioning

confidence: 99%

“…However, the reported LC-MS/MS run time was still up to 15 min (Quintela et al, 2004), which limits the analysis throughput when large-scale clinical samples need to be assayed. The latest LC-MS/MS report explored the extraction efficiency and recovery using tobulene-isoamylic alcohol, and the stability of the quality control samples undergoing three freeze/thaw cycles or set on a laboratory bench for 3 h (Jabor et al, 2005). However, long-term frozen-stored quality control (QC) sample stability, processed sample stability, dilution integrity, batch size and regular QC sample room temperature 24 h stability remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

Li¹,

Luo²,

Smith³

et al. 2007

Biomedical Chromatography

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A sensitive and simple liquid chromatography-tandem mass spectrometry method for the determination of midazolam and 1'-hydroxymidazolam in human plasma has been developed and validated with a dynamic range of 0.1-250 ng/mL. The analysis was based on semi-automated liquid-liquid extraction followed by evaporation of the extraction solvent, reconstitution and chromatography on a reversed-phase C(18) column. The mobile phase consists of 5 mm ammonium acetate and methanol and runs in gradient at a flow rate of 0.25 mL/min with column temperature of approximately 20 degrees C. The entire column effluent was transferred into the LC-MS/MS interface operated in positive electrospray ionization mode. The chromatographic run time was 4.3 min per injection, with retention times for midazolam, 1'-hydroxymidazolaml and the internal standard, triazolam, of 2.5, 2.3 and 2.1 min, respectively. The intra-day and inter-day precision (RSD %) and accuracy (bias %) of the quality control samples were <15.0% and within +/-13%, respectively. The current method has been applied to a clinical drug-drug interaction study in human.

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Section: Lc-ms/msmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

Li¹,

Luo²,

Smith³

et al. 2007

Biomedical Chromatography

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“…One of the advantages of this method is the quantifi cation of HMG without deglucuronidation, which reduces processing time and minimizes sample volume. HMG quantifi cation is hardly mentioned in previously published methods (Kumar et al, 2007;Link et al, 2007;Li et al, 2007;Jabor et al, 2005). The combined analysis of multiple drugs in itself reduces the required sample volume as well, especially in combination with a micro-SPE manifold that allows samples of 50 μL or less with minimal elution volumes.…”

Section: Methods Performancementioning

confidence: 99%

Quantification of midazolam, morphine and metabolites in plasma using 96‐well solid‐phase extraction and ultra‐performance liquid chromatography–tandem mass spectrometry

Ahsman

Nagel

Mathôt

2010

Biomedical Chromatography

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Currently, pharmacokinetic-pharmacodynamic studies of sedatives and analgesics are performed in neonates and children to find suitable dose regimens. As a result, sensitive assays using only small volumes of blood are necessary to determine drug and metabolite concentrations. We developed an ultra-performance liquid chromatographic method with tandem mass spectrometry detection for quantification of midazolam, 1-hydroxymidazolam, hydroxymidazolamglucuronide, morphine, morphine-3-glucuronide and morphine-6-glucuronide in 100 microL of plasma. Cleanup consisted of 96 wells micro-solid phase extraction, before reversed-phase chromatographic separation (ultra-performance liquid chromatography) and selective detection using electrospray ionization tandem mass spectrometry. Separate solid-phase extraction methods were necessary to quantify morphine, midazolam and their metabolites because of each group's physicochemical properties. Standard curves were linear over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 85-115% (of nominal concentration using a fresh calibration curve) and 15% (coefficient of variation, CV) respectively. Recoveries were >80% for all analytes, with interbatch CVs (as a measure of matrix effects) of less than 15% over six batches of plasma. Stability in plasma and extracts was sufficient, allowing large autosampler loads. Runtime was 3.00 min per sample for each method. The combination of 96-well micro-SPE and UPLC-MS/MS allows reliable quantification of morphine, midazolam and their major metabolites in 100 microL of plasma.

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“…Midazolam is a widely used short-acting benzodiazepine with hypnotic, sedative, anticonvulsant, muscle-relaxant, amnesic, and anxiolytic properties (Jabor et al, 2005;Emoto and Iwasaki, 2007). Midazolam is preferred over diazepam because of its shorter induction and recovery times and its marked amnesic properties (Lichtenstein et al, 2008;Riphaus et al, 2009;Correia et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The effects of midazolam and etomidate on the antioxidant system in the rat liver

Bayram¹,

Öncü²,

Uz³

et al. 2015

Turk J Biol

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This study was conducted to investigate the histopathological and biochemical effects of midazolam and etomidate, which are intravenous anesthetics used in surgical operations, on rat liver. There were 3 study groups each consisting of 9 animals: the control, midazolam, and etomidate groups. Midazolam and etomidate were administered 10 times with 1-day intervals. At the end of the study, tissues were taken for histological examination and biochemical analysis. We determined superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels in the liver. There was a slight increase in MDA level in the midazolam-exposed group when compared with the controls, and this was not statistically significant. However, SOD and CAT activities were significantly increased in the midazolam group. We found slight damage in histological sections in parallel to biological findings. MDA levels were significantly increased in the etomidate group and SOD and CAT activities were also prominent in this group. More histological changes like hepatocyte degeneration, vascular congestion, and mononuclear cell infiltration were observed in the etomidate group and this was statistically significant. We can say that these intravenous anesthetic agents may cause dose-dependent damage in tissue. Therefore, we think that one must be cautious of the administration duration and dose levels of anesthetics during surgical operations.

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A highly sensitive LC–MS–MS assay for analysis of midazolam and its major metabolite in human plasma: Applications to drug metabolism

Cited by 44 publications

References 20 publications

Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

Quantification of midazolam, morphine and metabolites in plasma using 96‐well solid‐phase extraction and ultra‐performance liquid chromatography–tandem mass spectrometry

The effects of midazolam and etomidate on the antioxidant system in the rat liver

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