Liquid Chromatographic Determination of Lipophilicity with Application to a HomologousSeries of Barbiturates

Toon, S.; Mayer, Joachim M.; Rowland, Malcolm

doi:10.1002/jps.2600730511

Cited by 15 publications

(2 citation statements)

References 29 publications

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“…Reverse‐phase high‐performance liquid chromatography (HPLC) partitions analytes based, in part, on polarity 20 . This methodology, as applied in previous studies, 21,22 was updated using contemporary HPLC analytical column technology.…”

Section: Methodsmentioning

confidence: 99%

“…Reverse-phase high-performance liquid chromatography (HPLC) partitions analytes based, in part, on polarity. 20 This methodology, as applied in previous studies, 21,22 was updated using contemporary HPLC analytical column technology. The system consisted of an Agilent 1100 Series isocratic HPLC (Agilent Technologies, Boston, MA, USA), a Phenomenex Synergi Hydro.…”

Section: Hplc Retention Index In Vitromentioning

confidence: 99%

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Effect of lipophilicity on drug distribution and elimination: Influence of obesity

Bruno¹,

Harmatz

Duan

et al. 2021

Brit J Clinical Pharma

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For a given passively-distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, V d ) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in V d associated with obesity across a series of drugs. Methods: Cohorts of normal-weight control and obese subjects received single doses of drugs ranging from hydrophilic (acetaminophen, salicylate) to lipophilic (imipramine, verapamil). Lipid solubility was measured by the log-transformed values of the high-pressure liquid chromatographic (HPLC) retention index (Log 10 (HPLC)), and the octanol-water partition coefficient (LogP).Results: Among normal-weight controls, V d normalized for protein binding was highly correlated with Log 10 (HPLC) (R 2 = .65) and with LogP (R 2 = .78). V d of all drugs was increased in the obese cohort, but the relative increase (compared to controls) for individual drugs was disproportionately greater as lipid solubility increased. Since clearance was unrelated to lipophilicity, the increased V d produced a parallel disproportionate increase in elimination half-life in the obese cohort that was associated with Log 10 (HPLC) (R 2 = .62). Conclusion:Lipophilicity is a principal correlate of in vivo V d , as well as the increased V d of drugs in obese patients. The consequent prolongation of half-life in obesity has clinical safety implications in terms of delayed drug accumulation and washout during and after chronic dosage. The magnitude and importance of this effect for a given drug depends on the degree of obesity, as well as the lipid-solubility of the specific drug.

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Section: Methodsmentioning

confidence: 99%

Section: Hplc Retention Index In Vitromentioning

confidence: 99%

Effect of lipophilicity on drug distribution and elimination: Influence of obesity

Bruno¹,

Harmatz

Duan

et al. 2021

Brit J Clinical Pharma

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Relationship between Lipophilicity and Tubular Reabsorption for a Series of 5‐Alkyl‐5‐ethylbarbituric Acids in the Isolated Perfused Rat Kidney Preparation

Mayer¹,

Hall

Rowland

1988

Journal of Pharmaceutical Sciences

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Determination of Octanol/Water Partition Coefficients of Certain Organophosphorus Compounds Using High‐Performance Liquid Chromatography

Krikorian

Chorn

King

1987

Quant. Struct.‐Act. Relat.

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Octanol/water partition coefficients (log P) for a series of dialkyl alkylphosphonates, dialkyl alkylphosphonothionates, and an alkyl alkylphosphinate have been estimated using reversed‐phase high‐performance liquid chromatography. The test compounds proved to be readily amenable to the chromatographic procedures employed, although the more lipophilic compounds appeared to be more tolerant to variations in the chromatographic conditions and methods of data handling than were the less lipophilic compounds with regard to the precision and accuracy of the log P values obtained from the retention data. The methodology was validated by carrying out shake‐flask experiments with two of the test samples. The rank order of log P values obtained was reasonably predictable, based on the sizes of the alkyl substituents present. The enhancement of lipophilic character attributable to replacement of oxygen by sulfur in the PO group is also evident from the results. The data for the phosphonates permit the calculation of a value for the hydrophobic fragmental constant for the OPO2 group (f = −2.79).

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Liquid Chromatographic Determination of Lipophilicity with Application to a HomologousSeries of Barbiturates

Cited by 15 publications

References 29 publications

Effect of lipophilicity on drug distribution and elimination: Influence of obesity

Effect of lipophilicity on drug distribution and elimination: Influence of obesity

Relationship between Lipophilicity and Tubular Reabsorption for a Series of 5‐Alkyl‐5‐ethylbarbituric Acids in the Isolated Perfused Rat Kidney Preparation

Determination of Octanol/Water Partition Coefficients of Certain Organophosphorus Compounds Using High‐Performance Liquid Chromatography

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