William LetterChiralizer Services, LLC · Analytical Chemistry, Medical Applications & Product Engineering/Design
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An expert scientific consultant, chromatographer, author, entrepreneur, inventor and hands-on technical scientist with 25+ years of applied knowledge, wisdom & skills in analytical chemistry for specialty chemical, pharmaceutical, analytical instrument, biopharm and medical product companies. Inventor of the Chiralizer, the LC Spiderling HPLC & SFC Column Selection Systems and many other products. LINKEDIN PROFILE: https://www.linkedin.com/in/wletter *Available for hourly & daily scientific consulting. Known to many as The HPLC WHISPERER™.
January 1993 - present
Chiralizer Services, LLC
- Senior Medicinal/Pharmaceutical Consultant. Provide advanced scientific training and troubleshooting courses worldwide in analytical instrument operation and analysis methods [Analytical & Prep HPLC, UHPLC, GPC, SEC, IEC, SFC, LC/MS, GC, GC/MS & CE; Chiral Chromatography; Light Scattering Detectors (e.g. MALS, CAD, ELSD); Amino Acid, Cannabinoids, Carbohydrates, Fats, Oils, Lipids, Vitamins, Polymers, Proteins & Peptides]. Design and fabricate novel commercial analytical and medical instruments.
June 1992 - January 1996
Pfizer (PKA: Wyeth Ayerst Research)
- To increase drug analysis sample throughput, I designed, set up and managed a fully automated high-speed analytical instrument facility which included several automated chiral & achiral method development systems (e.g. HPLC, LC-MS, GC-MS & CZE). Provided analysis training and results interpretation. Consulted on medicinal chemistry projects.
February 1990 - June 1992
Varex Corporation (A Division of Alltech Associates)
- Laboratory Manager
- Designed new HPLC products and accessories (e.g. Evaporative Light Scattering Detector); Over 50 new product app, tech notes and operator's manuals for LC, GC & ELSD; Presented technical talks & training worldwide; Managed contract analysis laboratory.
HPLC retention times must be reproducible from run to run. When problems occur, late, early or variable peak retention times may be observed. Common Reasons for HPLC Retention Time Drift, Variation or Change. This article presents several reasons why they may occur and what you can do to stabilize them.
"Carry-over" is a term used to describe a type of sample contamination which causes sample peaks to re-appear in later runs which do not actually contain the sample (e.g. blank runs). The contamination can last for several sequential runs, often decreasing in amount after each injection (which is a key observation when troubleshooting). When proper...
Chromatographers can use column selection and column switching valves to improve the development and performance of high performance liquid chromatography (HPLC) methods. This installment of "Sample Prep Perspectives" describes the use of multiport, high-pressure HPLC valves that help in many applications. These column-selection systems can screen,...
A rapid high-performance liquid chromatographic method for the separation and identification of several triglycerides in edible oil and fat samples using an evaporative light-scattering detector (ELSD) is described. A single 25 cm Hypersil C-18 column maintained at 35°C was used successfully to analyze and identify a variety of triglycerides from a...
A high-performance liquid chromatographic method for the separation and quantification of major natural phospholipid classes using an evaporative light-scattering detector is described. Separation and detection of cholesterol, palmitic acid, phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine and sphingomyelin was achieved in less tha...
The single most important component of any HPLC system is the Pump module. We often refer to it as "the heart of the HPLC system". You may have the most sensitive HPLC detector, the best column, a perfect method of analysis, but none of this will matter unless the HPLC pump(s) that provide mobile phase to the system operates perfectly, all of the t...
After developing several hundred successful chiral methods for different pharmaceutical compounds we began to explore other useful isocratic mobile phase solutions for use with the non-covalently bound Daicel columns. Specifically, the Chiralpak® AD and AS, as well as the Chiralcel® OD and OJ columns. We had already discovered that the mobile phase...
In this article, we will discuss how temperature fluctuations, inadequate mixing, degassing and flow cell contamination can result in excessive HPLC or UHPLC baseline noise and provide suggestions on how to reduce or eliminate them.
One common area that is often overlooked in the area of HPLC is that of connection fittings and tubing selection. Selection and installation of the correct HPLC fittings and tubing can help you avoid future problems while allowing your system to run at peak performance. Common types of high pressure chromatography fittings and tubing found in the l...
To verify correct detector wavelength accuracy of your HPLC UV / VIS module, it is periodically necessary to measure the wavelength accuracy against know standards using an appropriate SOP ("fit for purpose"). This may be required as part of a Performance Verification (PV), Installation Qualification (IQ) or Operational Qualification (OQ).
Obtaining accurate LC-MS (ESI) analysis data for your samples depends a great deal on your proficiency and skill as an instrument operator. It also depends on placing a great deal of importance in selecting and optimizing the LC-MS Electrospray Ionization Interface (ESI) voltage. To better understand why it is necessary to do so and how it effects...
Observations over several years that many chiral racemic compounds could be baseline resolved with a 100% ethanol mobile phase on chiral NP columns led us to investigate what other simple mostly alcohol based mobile phases might also work well? The mobile phase test group included: Methanol, 1, Butanol, 2-Butanol, 2-Propanol and Acetonitrile with a...
Diode-Array based Peak purity determination by HPLC is a qualitative assessment of the impurity profile of the sample. It is designed to reveal impurities, not prove peak purity. BTW: We really should rename it “Peak Spectral Impurity Assessment” because that is in fact what we are measuring. The algorithm used for Peak Purity determination is desi...
A preparative high-performance liquid chromatographic (HPLC) method, based on recycle chromatography, to separate vitamin D2 (ergocalciferol) from previtamin D is described. The method provides efficient separation by means of a mixture of methanol, acetonitrile and hexane as eluent on a reversed-phase C18 column. Scale-up to a 2-in. diameter colum...
Fat Soluble Vitamins, Retinol (A), Ergocalciferol (D2), Cholecalciferol (D3), Tocopherol (E) and Phylloquinone (K1) by HPLC on a C18 column with Acetonitrile/Water using an Evaporative Light Scattering Detector (ELSD). Analysis of simple sugars by HPLC on a RP-18 column with Methanol/ACN/Hexane with an Evaporative Light Scattering Detector (ELSD)....
A novel Evaporative Light-Scattering Detector (ELSD) is presented highlighting several advantages over more common UV/VIS and Refractive Index HPLC detectors. ELSD Application examples are presented which include: Carbohydrate, Lipid, Fatty Acids, Polymer, Surfactant, Amino Acids, Dextran, Sugars, Steroids, Vitamins, Histidine, Polystyrene, Tergito...
The procedures described in this technical note were specifically designed for use with the Varex model IIA ELSD. Proper use of any ELSD requires that an appropriate, highly volatile mobile phase is selected, the gas flow rate adjusted, the drift tube temperature and the signal to noise ratio of the sample are all optimized. This note provides a pr...