High‐throughput logP measurement using parallel liquid chromatography/ultraviolet/mass spectrometry and sample‐pooling

Zhao, Yining; Jona, Janan; Chow, David; Rong, Haojing; Semin, David; Xia, Xiaoyang; Zanon, Roger; Spancake, Chris; Maliski, Ed

doi:10.1002/rcm.749

Cited by 53 publications

(37 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shake-flask, microshake-flask, and chromatography retention are the most common methods for compound lipophilicity measurement and some of them could be used in a throughput mode [25][26][27][28][29][30][31]. Despite the availability of these assays, different instruments and multiple measurements are often needed to obtain LogP, LogD (pH) , and pK a values, separately.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of LogD, LogP, and pKa of Drugs by Using a Reverse Phase HPLC Coupled with a 96-Well Plate Auto Injector

Chiang

Hu²

2009

CCHTS

View full text Add to dashboard Cite

For years, the physicochemical properties of drug candidates have been used to predict their in vivo pharmacokinetic behaviors. Several theories and empirical correlations have been established by various researchers with the overall goal of expediting the drug candidate selection process, with greater confidence and faster turnaround. This study describes a 96-well reverse phase HPLC method, simultaneously determining LogD, LogP, and pK(a) values of drugs in a throughput mode. The LogD and LogP values of each compound were determined, based on the octanol-aqueous partitioning behavior of the charged and non-charged species under different pH values. The pK(a) value was determined by using the Polynomial fit between LogP and LogD and the equation LogD (pK(a)) approximately LogP-0.301. The advantages of this method are: low sample consumption, suitability for low solubility compounds, less restriction on compound purity, potential for higher throughput, precise data, and multiple determinations in one assay.

show abstract

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of LogD, LogP, and pKa of Drugs by Using a Reverse Phase HPLC Coupled with a 96-Well Plate Auto Injector

Chiang

Hu²

2009

CCHTS

View full text Add to dashboard Cite

show abstract

“…Subsequent papers demonstrate the use of MUX technology in the quantitative analysis of samples derived from rat [182] human [183], mouse, rat, rabbit and dog [184,185] plasmas and the analysis of rat liver microsomal samples [186]. Eightchannel MUX systems have also been employed for the determination of logP [187] and to carry out accurate mass measurements [188].…”

Section: Multiple Inletsmentioning

confidence: 98%

Fast LC/MS in the analysis of small molecules

Tiller

Romanyshyn

Neue

2003

Analytical and Bioanalytical Chemistry

View full text Add to dashboard Cite

Liquid chromatography-mass spectrometry (LC/MS) has become one of the most widely used analytical techniques in both qualitative and quantitative analysis of small molecules. Recently, with the increasing demand for ever-higher sample throughput, the use of faster chromatographic separations has become popular, along with other LC/MS methods that decrease analytical cycle-time. The burgeoning use of LC/MS has meant that the primary expertise of many practitioners today is not in the field of LC/MS, which has been facilitated by the ease-of-use of modern LC/MS systems. An examination of the current state of the literature, relating to "fast LC/MS", should serve well to those new to LC/MS, and should help them in the development of fast LC/MS methods that are effective in terms of both the chromatography and the utilization of the mass spectrometer. This review paper focuses on fast LC/MS analyses of small molecules that have been reported in peer-reviewed publications.

show abstract

“…Fluorescein sodium, which is freely soluble in water (0.1-1.0 g/mL) (36) and has a log P value of -1.52 (37), was chosen as a hydrophilic compound. Triamterene, a potassium-sparing diuretic with water solubility of 28 µg/mL (38) and log P value of 1.25 (39), was used as a fluorescent hydrophobic model compound. The fluorescent model substances were embedded in a blend of ammonio methacrylate copolymer type A and B (Eudragit RL/Eudragit RS, 3:7 ratio).…”

Section: Apparatus Design and Experimental Conditionsmentioning

confidence: 99%

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Seidlitz¹,

Nagel²,

Semmling³

et al. 2011

Dissolution Technol.

View full text Add to dashboard Cite

In vitro dissolution testing of drug-eluting stents (DES) poses a special challenge in terms of apparatus design due to the very specialized local treatment of the vessel wall in the immediate vicinity of the blood flowing through the vessel and the stent lumen. A vessel-simulating flow-through cell was designed to emulate the placement of a DES in vivo and the flow through the lumen in a simplified in vitro setup, which also allows for the examination of distribution processes. The method is based on the compendial flow-through cell apparatus (USP 4), which was modified by the addition of a hydrogel compartment that represents the vessel wall and the adaptation of the flow rate to the blood flow rate in the coronary vessels. A comparison of the dissolution and release results obtained with the vessel-simulating flow-through cell with standard paddle (USP 2) and flow-through cell (USP 4) apparatus methods shows that release from the coating was decelerated by embedding in the hydrogel in the adapted apparatus. Further experiments with both hydrophilic and hydrophobic fluorescent model compounds coated onto the stents were performed to investigate the effects of different method parameters and variations in the coating composition. While release and distribution of hydrophilic fluorescein sodium were dependent on the flow rate and implantation technique, release kinetics of hydrophobic triamterene were influenced by the coating thickness and the model substance content of the coating. These results illustrate the importance of choosing the correct apparatus design and test parameters adapted to biorelevant conditions for specialized dosage forms such as DES.

show abstract

High‐throughput logP measurement using parallel liquid chromatography/ultraviolet/mass spectrometry and sample‐pooling

Cited by 53 publications

References 19 publications

Simultaneous Determination of LogD, LogP, and pKa of Drugs by Using a Reverse Phase HPLC Coupled with a 96-Well Plate Auto Injector

Simultaneous Determination of LogD, LogP, and pKa of Drugs by Using a Reverse Phase HPLC Coupled with a 96-Well Plate Auto Injector

Fast LC/MS in the analysis of small molecules

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Contact Info

Product

Resources

About