Analytical Chemistry Lesson of the Day – Accuracy in Method Validation and Quality Assurance

In pharmaceutical chemistry, one of the requirements for method validation is accuracy, the ability of an analytical method to obtain a value of a measurement that is close to the true value. There are several ways of assessing an analytical method for accuracy.

1. Compare the value from your analytical method with an established or reference method.
2. Use your analytical method to obtain a measurement from a sample with a known quantity (i.e. a reference material), and compare the measured value with the true value.
3. If you don’t have a reference material for the second way, you can make your own by spiking a blank matrix with a measured quantity of the analyte.
4. If your matrix may interfere with the analytical signal, then you cannot spike a blank matrix as described in the third way.  Instead, spike your sample with an known quantity of the standard.  I elaborate on this in a separate tutorial on standard addition, a common technique in analytical chemistry for determining the quantity of a substance when matrix interference exists.  Standard addition is an example of the second way of assessing accuracy as I mentioned above.  You can view the original post of this tutorial on the official JMP blog.

New Job at the Bank of Montreal in Toronto

I have accepted an offer from the Bank of Montreal to become a Manager of Operational Risk Analytics and Modelling at its corporate headquarter office in Toronto.  Thus, I have resigned from my job at the British Columbia Cancer Agency.  I will leave Vancouver at the end of December, 2015, and start my new job at the beginning of January, 2016.

I have learned some valuable skills and met some great people here in Vancouver over the past 2 years.  My R programming skills have improved a lot, especially in text processing.  My SAS programming skills have improved a lot, and I began a new section on my blog to SAS programming as a result of what I learned.  I volunteered and delivered presentations for the Vancouver SAS User Group (VanSUG) – once on statistical genetics, and another on sampling strategies in analytical chemistry, ANOVA, and PROC TRANSPOSE.  I have thoroughly enjoyed meeting some smart and helpful people at the Data Science, Machine Learning, and R Programming Meetups.

I lived in Toronto from 2011 to 2013 while pursuing my Master’s degree in statistics at the  University of Toronto and working as a statistician at Predicum.  I look forward to re-connecting with my colleagues there.

Potato Chips and ANOVA, Part 2: Using Analysis of Variance to Improve Sample Preparation in Analytical Chemistry

In this second article of a 2-part series on the official JMP blog, I use analysis of variance (ANOVA) to assess a sample-preparation scheme for quantifying sodium in potato chips.  I illustrate the use of the “Fit Y by X” platform in JMP to implement ANOVA, and I propose an alternative sample-preparation scheme to obtain a sample with a smaller variance.  This article is entitled “Potato Chips and ANOVA, Part 2: Using Analysis of Variance to Improve Sample Preparation in Analytical Chemistry“.

If you haven’t read my first blog post in this series on preparing the data in JMP and using the “Stack Columns” function to transpose data from wide format to long format, check it out!  I presented this topic at the last Vancouver SAS User Group (VanSUG) meeting on Wednesday, November 4, 2015.

My thanks to Arati Mejdal, Louis Valente, and Mark Bailey at JMP for their guidance in writing this 2-part series!  It is a pleasure to be a guest blogger for JMP!

Vancouver SAS User Group Meeting – Wednesday, November 4, 2015

I am excited to present at the next Vancouver SAS User Group (VanSUG) meeting on Wednesday, November 4, 2015.  I will illustrate data transposition and ANOVA in SAS and JMP using potato chips and analytical chemistry.  Come and check it out!  The following agenda contains all of the presentations, and you can register for this meeting on the SAS Canada web site.  This meeting is free, and a free breakfast will be served in the morning.

Update: My slides from this presentation have been posted on the VanSUG web site.

Date: Wednesday, November 4, 2015

Place:

Ballroom West and Centre

Holiday Inn – Vancouver Centre

V5Z 3Y2

(604) 879-0511

Agenda:

8:30am – 9:00am: Registration

9:00am – 9:20am: Introductions and SAS Update – Matt Malczewski, SAS Canada

9:20am – 9:40am: Lessons On Transposing Data, Sampling & ANOVA in SAS & JMP – Eric Cai, Cancer Surveillance & Outcomes, BC Cancer Agency

10:20am – 10:30am: A Beginner’s Experience Using SAS – Kim Burrus, Cancer Surveillance & Outcomes, BC Cancer Agency

10:30am – 11:00am: Networking Break

11:00am – 11.20am: Using SAS for Simple Calculations – Jay Shurgold, Rick Hansen Institute

11:20am – 11:50am: Yes, We Can… Save SAS Formats – John Ladds, Statistics Canada

11:50am – 12:20pm: Reducing Customer Attrition with Predictive Analytics – Nate Derby, Stakana Analytics

12:20pm – 12:30pm: Evaluations, Prize Draw & Closing Remarks

If you would like to be notified of upcoming SAS User Group Meetings in Vancouver, please subscribe to the Vancouver SAS User Group Distribution List.

Analytical Chemistry Lesson of the Day – Linearity in Method Validation and Quality Assurance

In analytical chemistry, the quantity of interest is often estimated from a calibration line.  A technique or instrument generates the analytical response for the quantity of interest, so a calibration line is constructed from generating multiple responses from multiple standard samples of known quantities.  Linearity refers to how well a plot of the analytical response versus the quantity of interest follows a straight line.  If this relationship holds, then an analytical response can be generated from a sample containing an unknown quantity, and the calibration line can be used to estimate the unknown quantity with a confidence interval.

Note that this concept of “linear” is different from the “linear” in “linear regression” in statistics.

This is the the second blog post in a series of Chemistry Lessons of the Day on method validation in analytical chemistry.  Read the previous post on specificity, and stay tuned for future posts!

Analytical Chemistry Lesson of the Day – Specificity in Method Validation and Quality Assurance

In pharmaceutical chemistry, one of the requirements for method validation is specificity, the ability of an analytical method to distinguish the analyte from other chemicals in the sample.  The specificity of the method may be assessed by deliberately adding impurities into a sample containing the analyte and testing how well the method can identify the analyte.

Statistics is an important tool in analytical chemistry, and, ideally, there is no overlap in the vocabulary that is used between the 2 fields.  Unfortunately, the above definition of specificity is different from that in statistics.  In a previous Machine Learning and Applied Statistics Lesson of the Day, I introduced the concepts of sensitivity and specificity in binary classification.  In the context of assessing the predictive accuracy of a binary classifier, its specificity is the proportion of truly negative cases among the classified negative cases.

Analytical Chemistry Lesson of the Day – Method Validation in Quality Assurance

When developing any method in analytical chemistry, it must meet several criteria to ensure that it accomplishes its intended objective at or above an acceptable standard.  This process is called method validation, and it has the following criteria* in the pharmaceutical industry:

• specificity
• linearity
• accuracy
• precision
• range
• limit of detection
• limit of quantitation
• robustness**

As I will note in future Chemistry Lessons of the Day, these words are used differently between statistics and chemistry.

*These criteria are taken from Page 723 of the 6th edition of “Quantitative Chemical Analysis” by Daniel C. Harris (2003).

**The Food and Drug Administration does not list robustness as a typical characteristic of method validation.  (See Section B on Page 7 of its “Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics“.)  However, it does mention robustness several times as an important characteristic that “should be evaluated” during the “early stages of method development”.

Determining chemical concentration with standard addition: An application of linear regression in JMP – A Guest Blog Post for the JMP Blog

I am very excited to announce that I have been invited by JMP to be a guest blogger for its official blog!  My thanks to Arati Mejdal, Global Social Media Manager for the JMP Division of SAS, for welcoming me into the JMP blogging community with so much support and encouragement, and I am pleased to publish my first post on the JMP Blog!  Mark Bailey and Byron Wingerd from JMP provided some valuable feedback to this blog post, and I am fortunate to get the chance to work with and learn from them!

Following the tradition of The Chemical Statistician, this post combines my passions for statistics and chemistry by illustrating how simple linear regression can be used for the method of standard addition in analytical chemistry.  In particular, I highlight the useful capability of the “Inverse Prediction” function under “Fit Model” platform in JMP to estimate the predictor given an observed response value (i.e. estimate the value of $x_i$ given $y_i$).  Check it out!

Discovering Argon with the 2-Sample t-Test

I learned about Lord Rayleigh’s discovery of argon in my 2nd-year analytical chemistry class while reading “Quantitative Chemical Analysis” by Daniel Harris.  (William Ramsay was also responsible for this discovery.)  This is one of my favourite stories in chemistry; it illustrates how diligence in measurement can lead to an elegant and surprising discovery.  I find no evidence that Rayleigh and Ramsay used statistics to confirm their findings; their paper was published 13 years before Gosset published about the t-test.  Thus, I will use a 2-sample t-test in R to confirm their result.

Photos of Lord Rayleigh

Source: Wikimedia Commons