CAS 1001083-56-2 Zaleplon-d5 - Analytical Products / Alfa Chemistry

CAT	APB1001083562
CAS	1001083-56-2
Molecular Weight	310.37
Molecular Formula	C17H10D5N5O

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Case Study

Synthesis and Application of Zaleplon-d5 as an Internal Standard for GC-MS Analysis

Shaikh, Ajam C., and Chinpiao Chen. "Synthesis of deuterium-labeled zaleplon-d5 as an internal standard." Journal of Labelled Compounds and Radiopharmaceuticals: The Official Journal of the International Isotope Society 51.1 (2008): 72-76.

Zaleplon-d5, a stable isotope-labeled internal standard, plays a crucial role in the identification and quantification of zaleplon in forensic and toxicological analysis. Due to the controlled nature of zaleplon and its potential for abuse, accurate detection methods are essential. Gas chromatography-mass spectrometry (GC-MS) is widely employed for this purpose, necessitating the use of reliable internal standards.
This study presents a robust synthesis of zaleplon-d5, ensuring high yield and purity. Initial synthetic routes involving the alkylation of acetamide 7 with ethyl iodide-d5 resulted in poor yields and challenging purification. An optimized approach, inspired by Dusza et al., improved the process significantly. Beginning with commercially available 30-nitroacetophenone (1), the synthesis proceeded through reduction to 30-aminoacetophenone (9), followed by acylation to acetamide (10). Subsequent treatment with N,N-dimethylformamide dimethylacetal yielded enamide (11), which was efficiently alkylated using ethyl iodide-d5 and sodium hydride to form N-ethylated enamide (12). The final coupling with 5-aminopyrazole (4) under mild aqueous acidic conditions produced zaleplon-d5 (8) with an impressive 85% yield.
The availability of zaleplon-d5 enables precise quantification of zaleplon in biological samples, enhancing the reliability of forensic toxicology assessments. Its high-yield synthesis offers a cost-effective solution for laboratories, facilitating accurate drug monitoring and regulatory compliance.

Zaleplon-d5: An Essential Internal Standard for LC-MS/MS Quantification of Z-Drugs in Dried Blood Spots

Déglon, Julien, et al. Bioanalysis 4.11 (2012): 1337-1350.

Zaleplon-d5, a stable isotope-labeled analogue of zaleplon, serves as a crucial internal standard in the quantitative analysis of zaleplon and related Z-drugs via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study highlights its application in an optimized dried blood spot (DBS) sampling method, which provides a cost-effective and efficient alternative to conventional plasma analysis.
A simple offline sample preparation strategy was developed, where a 5-µL DBS was directly infused into 100 µL of methanol in an LC vial. The method effectively extracted zaleplon and other target analytes, ensuring minimal solvent and consumable usage while maintaining analytical accuracy. To enhance method reliability, zaleplon-d5, along with other deuterated standards, was incorporated at a defined concentration, compensating for matrix effects and instrumental variability.
Validation of the approach demonstrated high sensitivity and precision across therapeutic concentration ranges, supporting its applicability in forensic and clinical toxicology. The integration of zaleplon-d5 as an internal standard not only improved quantitation accuracy but also facilitated rapid screening of benzodiazepines and Z-drugs in DBS samples, even with non-specialized autosamplers.

Zaleplon-d5: A Stable Isotope-Labeled Internal Standard for Ultra-Sensitive Hair Analysis of Sedative-Hypnotics

Wille, S. M., et al. Therapeutic drug monitoring 37.5 (2015): 600-608.

Zaleplon-d5, a deuterium-labeled analogue of zaleplon, serves as a crucial internal standard in ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the quantification of sedative-hypnotics in biological matrices. In a validated analytical method for detecting benzodiazepines and Z-drugs in hair, zaleplon-d5 was employed to ensure high precision and accuracy.
This method involved decontaminating and pulverizing 20 mg of hair samples before extracting analytes with methanol and sonicating for two hours at 45°C. Liquid-liquid extraction with 1-chlorobutane enhanced drug recovery, followed by evaporation and reconstitution in methanol prior to UHPLC-MS/MS injection. A gradient elution system using 0.1% formic acid in water and methanol facilitated the separation of 29 analytes within seven minutes.
Zaleplon-d5, along with other isotope-labeled internal standards, was used to correct for matrix effects and instrumental variations, ensuring reliable quantification. The method demonstrated lower limits of quantification (0.5-5 pg/mg), with calibration curves displaying strong linearity (up to 620 pg/mg). Extraction efficiency ranged from 19% to 82%, with minimal matrix interferences. The validated technique was successfully applied to workplace drug testing, identifying zaleplon and its metabolites in authentic hair samples.