Discovering drugs from natural products is challenging. It involves describing the bioactive compound, its pharmacological and characterization investigations, and phytochemical analysis. Successful natural product analysis depends on the resources available for finding and discovering new drug compounds for human resources. Over the years, natural products have been the primary source of therapeutic agents and hence, play a critical role in developing and accelerating scientific endeavors.
Natural product analysis and drug discovery require robust compounds with the necessary bioavailability profile of the drug to accelerate the compound from initial screening analysis to subsequent clinical studies. Today, drug developers have numerous bioanalytical techniques for exploring natural products and drug discovery analysis. Liquid chromatography-mass spectrometry (LC-MS) is one such robust technique. The current article discusses the role of LC-MS labs in natural product analysis. However, LC-MS method development and validation will remain crucial for delivering reliable and robust results.
LC-MS labs for natural product analysis
HPLC coupled with a mass spectrometer is a powerful tool offering higher sensitivity and selectivity. Electrospray ionization is a common technique used in LC-MS systems. LC-MS labs perform both positive and negative ionization to obtain a comprehensive profile. Electrospray ionization employs a high electric field to generate charged droplets in a liquid solution. This electric field ultimately forms the gas phase ions. The primary benefit of the electrospray ionization technique is that it does not require derivatization, can ionize compounds with large masses, provides excellent quantitative analysis and higher sensitivity, and is suitable for nonvolatile and polar compounds.
Besides the electrospray ionization (ESI) technique, LC-MS labs also employ other solution-based ionization techniques, including atmospheric pressure chemical ionization, atmospheric pressure photoionization, and NanoESI. NanoESI offers enhanced sensitivity and a broader dynamic range. This technique decreases the chemical noise and improves chromatography separations.
Chip-based Nano electrospray system is another strategy that improves sensitivity and reduces matrix effects. Moreover, strategies such as atmospheric pressure chemical ionization and atmospheric pressure photoionization are relatively robust and tolerant towards high buffer concentrations with little to no fragmentations. Hence, they are increasingly used to evaluate thermally stable and nonpolar compounds such as lipids.
Often, LC-MS labs employ capillary high-performance liquid chromatography-mass spectrometry. This technique provides higher peak capacity, higher chromatography resolution, and enhanced signal-to-noise ratio. Additionally, this technique requires less study sample, and hence, capillary HPLC-MS can provide a large number of data output.
Another technique, namely ultra-performance LC-MS, is a combination of a chromatography system and reverse phase packing material with an operational capacity of 6000 to 15000 PSI. As ultra-performance LC-MS reduces band broadening, it offers a higher signal-to-noise ratio and increases assay sensitivity. This feature results in better chromatography peak resolution and enhanced sensitivity and speed in analyzing complex mixture separations. Moreover, with increased resolution, ultra-performance LC-MS does not have the issues of ion separation with coeluting peaks.
With increasing interest in herbal formulations having minimum side effects, LC-MS labs are becoming a focal point in the exploration of the medicinal and biological properties of natural products. However, the continued success of natural product analysis and drug discovery will largely depend on robust LC-MS analysis.