Determination of midazolam and 1-hydroxymidazolam from plasma by gas chromatography coupled to methane negative chemical ionization mass spectrometry after sublingual administration of midazolam

Kaartama, Ruut; Jarho, Pekka; Savolainen, Jouko; Kokki, Hannu; Lehtonen, Marko

doi:10.1016/j.jchromb.2011.04.009

Cited by 18 publications

(17 citation statements)

References 36 publications

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“…The concentration of midazolam and its metabolite 19-hydroxymidazolam were determined by LC-MS/MS (Dostalek et al, 2010;Zhang et al, 2010;Kaartama et al, 2011). Sample preparation was performed by protein precipitation with acetonitrile containing internal standards [ 2 H 4 ]midazolam and [ 2 H 4 ]19-hydroxymidazolam.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Endogenous 4β-Hydroxycholesterol with Midazolam as Markers for CYP3A4 Induction by Rifampicin

et al. 2013

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CYP3A4, considered the most important enzyme in drug metabolism, is often involved in drug-drug interactions. When developing new drugs, appropriate markers for detecting CYP3A4 induction are needed. Our study compared endogenously formed 4β-hydroxycholesterol with the midazolam clearance in plasma and the 6β-hydroxycortisol/cortisol ratio in urine as markers for CYP3A4 induction. To this end, we performed a clinical trial in which 24 healthy subjects were randomized to 10, 20, or 100 mg daily doses of rifampicin for 14 days (n = 8 in each group) to achieve a low and moderate CYP3A4 induction. The CYP3A4 induction could be detected even at the lowest dose of rifampicin (10 mg) via the estimated midazolam clearance, the 4β-hydroxycholesterol ratio (both P < 0.01), and the 6β-hydroxycortisol ratio (P < 0.05). For the three dosing groups (10, 20, and 100 mg), the median fold induction from baseline was 2.0, 2.6, and 4.0 for the estimated midazolam clearance; 1.3, 1.6, and 2.5 for the 4β-hydroxycholesterol/cholesterol ratio; and 1.7, 2.9, and 3.1 for the 6β-hydroxycortisol/cortisol ratio. In conclusion, the 4β-hydroxycholesterol ratio is comparable to midazolam clearance as a marker of CYP3A4 induction, and each may be used to evaluate CYP3A4 induction in clinical trials evaluating drug-drug interactions for new drugs.

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Section: Methodsmentioning

confidence: 99%

Comparison of Endogenous 4β-Hydroxycholesterol with Midazolam as Markers for CYP3A4 Induction by Rifampicin

et al. 2013

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“…As Figure 3 reflects conventional LLE [31,32], (ethyl acetate [33], 0.2% formic acid [34] etc.) or SPE [35][36][37][38] are still widely used by most researchers as isolation steps with no obvious relative advantages. Methanol extraction procedure for benzodiazepines determination is useful for forensic toxicological purposes and in case of a small amount of hair available a phosphate extraction is preferred [39].…”

Section: Extraction Techniquesmentioning

confidence: 99%

“…A mixed-mode cation-exchange polymeric sorbent [37,46,47] was used for solid phase extraction of benzodiazepines in human whole blood. Benzodiazepines can be extracted from biological fluids, such as blood and urine using QuEChERS ("catchers") [48], a novel sample preparation technique used for high aqueous content samples.…”

Section: Extraction Techniquesmentioning

confidence: 99%

“…Comparision among the methods published Gas chromatography: Gas chromatography (GC) still offers the best means to confirm benzodiazepines. Most of these methods derivatized the benzodiazepines with silylating reagents [32,37] to improve spectral definition and to reduce on-column thermal degradation. Two stages of derivatization using tetramethylammonium hydroxide and propyliodide (propylation), as well as a mixture of triethylamine:propionic anhydride (propionylation) were performed for the simultaneous determination of the 23 most commonly used benzodiazepines in blood [72].…”

Section: High Performance Liquid Chromatography (Hplc)mentioning

confidence: 99%

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An Overview on Total Analytical Methods for the Detection of 1,4-Benzodiazepines

Uddin¹,

Victoria²,

Samanidou³

et al. 2014

Pharm Anal Acta

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“…The solubility in water is approximately 10.3 mg.mL -1 (pH 3.4, 25°C) (7). MDZ is available commercially in tablet and injection forms (8). Several methods by LC are described for MDZ quantification and its metabolites in biological matrices of humans, rats and rabbits plasma (9,10), as well methods to evaluate the quality of pharmaceutical formulations, compiled in the review (11).…”

Section: Introductionmentioning

confidence: 99%

Stability-Indicating Lc Method for the Quantification of Midazolam Active Pharmaceutical Ingredient and in Pharmaceutical Formulations

et al. 2018

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A stability-indicating LC method was validated for the quantification of midazolam (MDZ) active pharmaceutical ingredient (API) and in pharmaceutical formulations. Isocratic chromatography was performed on C18 column with mobile phase containing methanol/acetonitrile/water (45:35:20 v/v/v) with 0.4% of triethylamine pH 6.5. The validation included specificity, linearity, accuracy, precision and robustness. In specificity, after acid, basic, neutral, oxidant and thermal degradation, it was found that the concentration of MDZ decreased substantially, with the appearance of peaks representatives of the degradation products, proving the stability-indicating power of the method. The response was linear in the range 50.0 – 250.0 µg.mL-1, with 11.73 µg.mL-1 and 3.87 µg.mL-1 as LOQ and LOD, respectively. Recoveries ranged between 98.68 and 100.41%. The relative standard deviation values for intra and interday precision were 1.11%, 0.82% and 1.47%, respectively. The tablets and injections containing MDZ were approved in the assay and content uniformity. The method can be adopted by pharmacopeias and for routine quality control for analysis of MDZ API, tablets and injection.

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Determination of midazolam and 1-hydroxymidazolam from plasma by gas chromatography coupled to methane negative chemical ionization mass spectrometry after sublingual administration of midazolam

Cited by 18 publications

References 36 publications

Comparison of Endogenous 4β-Hydroxycholesterol with Midazolam as Markers for CYP3A4 Induction by Rifampicin

Comparison of Endogenous 4β-Hydroxycholesterol with Midazolam as Markers for CYP3A4 Induction by Rifampicin

An Overview on Total Analytical Methods for the Detection of 1,4-Benzodiazepines

Stability-Indicating Lc Method for the Quantification of Midazolam Active Pharmaceutical Ingredient and in Pharmaceutical Formulations

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