Dataset Information

LC-MS/MS Method for Rapid Quantification of Progesterone in Rabbit Plasma and Its Application in a Pharmacokinetic Study of the Transdermal Formulation.

ABSTRACT: A rapid and effective method using QuEChERS-based sample preparation procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has been developed and validated to determine progesterone in rabbit plasma. The analyte was extracted from plasma by acetonitrile with phase partitioning by a mixture of magnesium sulfate and sodium chloride. The supernatant was then directly injected into LC-MS/MS in a positive electrospray ionization mode and quantified using progesterone-d9 as the internal standard. The method linearity was in the range from 1?ng/mL (LOQ) to 200?ng/mL. Method recovery was from 86.0% to 103%, and repeatability was lower than 5.5%. The plasma sample was stable for 12 weeks stored at 18?±?2°C. This method was applied to quantify progesterone in rabbit plasma in a pharmacokinetic study of two transdermal formulations: a reference drug and a eutectic-hydrogel system. The data indicate that the eutectic-hydrogel system's bioavailability was 1.5 times better than that of the reference drug, and the transdermal system is a potential drug delivery system for progesterone.

SUBMITTER: Tran CS

PROVIDER: S-EPMC7647766 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

LC-MS/MS Method for Rapid Quantification of Progesterone in Rabbit Plasma and Its Application in a Pharmacokinetic Study of the Transdermal Formulation.

Tran Cao-Son CS Bui Quang-Dong QD Nguyen Ngoc-Tho Thi NT Dao Minh-Hanh MH Nguyen Thach-Tung TT

Journal of analytical methods in chemistry 20201030

A rapid and effective method using QuEChERS-based sample preparation procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has been developed and validated to determine progesterone in rabbit plasma. The analyte was extracted from plasma by acetonitrile with phase partitioning by a mixture of magnesium sulfate and sodium chloride. The supernatant was then directly injected into LC-MS/MS in a positive electrospray ionization mode and quantified using progesterone-d9 as ...[more]

PMID: 33178479

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Project description:Assessing human exposure to commonly used, highly toxic, but non-persistent organophosphates (OPs) is challenging because these toxicants are readily biotransformed into dialkyl phosphates (DAPs) and other metabolites. Growing hair accumulates toxicants and their metabolites, which makes hair a valuable non-invasively sampled matrix that can be used to retrospectively examine chemical exposure. However, the efficient quantification of hydrophilic DAP compounds in hair is challenging due to complex hair matrix effects. To improve upon existing methods, we first examined the acid dissociation constants (pKa) of DAPs and amino acids (major components in hair) and identified the best pH conditions for minimizing matrix effects. We hypothesized that under basic pH conditions DAPs and amino acids would be negatively charged and have weak interactions favorable to DAP dissociation from the matrix. To test this, we compared the efficiency of various pH conditions of suitable solvents to extract six DAPs from hair samples, and we quantified these DAPs using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). As expected, a basic extraction (methanol with 2% NH4OH) approach had the highest extraction efficiency and yielded satisfactory recoveries for all six DAPs (72%-152%) without matrix effects. Additionally, the alkaline extract can be directly injected into the LC-MS/MS. This relatively rapid and simple procedure allowed us to process up to 90 samples per week with reproducible results. To our knowledge, this is the first method to quantify all six DAPs simultaneously in hair using LC-MS/MS with electrospray ionization (ESI) in negative ion mode. Finally, we demonstrated the feasibility of measuring DAP levels in hair samples from patients affected with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease potentially linked to OP exposure. Due to our optimized solvent extraction process, the method we have developed is compatible with the rapidity and sensitivity needed for hair analysis applied to population biomonitoring.

Dataset Information

LC-MS/MS Method for Rapid Quantification of Progesterone in Rabbit Plasma and Its Application in a Pharmacokinetic Study of the Transdermal Formulation.

Publications

LC-MS/MS Method for Rapid Quantification of Progesterone in Rabbit Plasma and Its Application in a Pharmacokinetic Study of the Transdermal Formulation.

Similar Datasets

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