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Simultaneous Determination of Safingol and d-erythro-Sphinganine in Human Plasma by LC with Fluorescence Detection |
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| Authors: | Joo-Sang Lee Hardeep Singh Barry J Maurer C Patrick Reynolds Min H Kang |
| Institution: | 1. Cancer Center, Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 6540, Lubbock, TX, 79430, USA 2. Department of Pharmacology, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 6540, Lubbock, TX, 79430, USA 3. Department Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 6540, Lubbock, TX, 79430, USA 4. Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 6540, Lubbock, TX, 79430, USA |
| Abstract: | l-threo-Sphinganine (safingol) is a putative synthetic sphingosine kinase inhibitor currently being tested in clinical trials as an anticancer agent. To enable defining the pharmacokinetic properties of safingol in humans, we developed a sensitive analytical method to simultaneously quantitate safingol and its naturally-occurring diastereomer, d-erythro-sphinganine in human plasma. Of the two different fluorogenic derivatization agents (NDA and OPA) and several pH conditions compared for the derivatization, we found that NDA derivatization achieved more than 20 times greater sensitivity compared with OPA derivatization, and pH 9.0 showed the highest sensitivity for both compounds. An analytical method for liquid chromatography (LC) with a fluorescence detector (FLD) was developed and validated with calibration curve ranges of 20–1,000 ng mL?1 for safingol and d-erythro-sphinganine. Our LC-FLD method using NDA-derivatization enabled simultaneous quantification of safingol and its naturally-occurring diastereomer, d-erythro-sphinganine with satisfactory sensitivity in human plasma. |
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